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Inflammatory chemokines in cancer growth and progression

  • Barrett J. Rollins
    Correspondence
    Tel.: +1 617 632 3896; fax: +1 617 632 5998.
    Affiliations
    Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
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      Abstract

      Leukocyte infiltration is a cardinal feature of almost all cancers. Chemokines are generally responsible for eliciting local accumulation of inflammatory cells and they appear to play the same role in the formation of peri- and intra-tumoural infiltrates. Chronic inflammation predisposes to cancer formation and progression, and it is likely that the chemokine system contributes to this process. In part, this may be a consequence of its ability to attract mononuclear cells to cancer sites, where they provide growth or angiogenic factors that enhance cancer development. However, accumulating evidence also points to a direct effect of chemokines on cancer cells that express chemokine receptors. In particular, some chemokines can activate anti-apoptotic pathways in these cells. By either mechanism, tumour cells that secrete and/or respond to chemokines would have a selective advantage. This provides another example of cancer’s ability to co-opt host systems in order to promote tumour progression.

      Keywords

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      References

        • Virchow R.
        Die krankhaften Geschwulste. Dreißig Vorlesungen, gehalten während des Wintersemesters 1862–1863 an der Universität zu Berlin.
        in: Vorlesungen uber Pathologie. Verlag von August Hirschwald, Berlin1863
        • Waldeyer H.W.G.
        Die entwicklung der carcinome.
        Virchows Arch Path Anat. 1872; : 55-67
        • Ehrlich P.
        Experimentelle studien an mäustumoren.
        Zeitschr f Krebsforschung. 1907; 5: 59-81
        • Russell B.R.G.
        The nature of resistance to the inoculation of cancer.
        Third Sci Rep ICRF. 1908; 3: 341-358
        • Da Fano C.
        A cytological analysis of the reaction in animals resistant to implanted carcinomata.
        Fifth Sci Rep ICRF. 1911; 5: 57-75
        • Berg J.W.
        Inflammation and prognosis in breast cancer: a search for host resistance.
        Cancer. 1959; 12: 714-720
      1. Black MM, Opler SR, Speer FD. Survival in breast cancer cases in relation to the structure of the primary tumor and regional lymph nodes. Surg Gynecol Obstet 1055;100:543–551.

        • Eccles S.A.
        • Alexander P.
        Macrophage content of tumors in relation to metastatic spread and host immune reaction.
        Nature. 1974; 250: 667-669
        • Balkwill F.
        • Charles K.A.
        • Mantovani A.
        Smoldering and polarized inflammation in the initiation and promotion of malignant disease.
        Cancer Cell. 2005; 7: 211-217
        • Zlotnik A.
        • Yoshie O.
        Chemokines: a new classification system and their role in immunity.
        Immunity. 2000; 12: 121-127
        • Matsushima K.
        • Larsen C.G.
        • DuBois G.C.
        • Oppenheim J.J.
        Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line.
        J Exp Med. 1989; 169: 1485-1490
        • Bottazzi B.
        • Walter S.
        • Govoni D.
        • Colotta F.
        • Mantovani A.
        Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma.
        J Immunol. 1992; 148: 1280-1285
        • Rollins B.J.
        • Sunday M.E.
        Suppression of tumor formation in vivo by expression of the JE gene in malignant cells.
        Mol Cell Biol. 1991; 11: 3125-3131
        • Laning J.
        • Kawasaki H.
        • Tanaka E.
        • Luo Y.
        • Dorf M.E.
        Inhibition of in vivo tumor growth by the beta chemokine, TCA3.
        J Immunol. 1994; 153: 4625-4635
        • Sharma S.
        • Stolina M.
        • Luo J.
        • Strieter R.M.
        • Burdick M.
        • Zhu L.X.
        • et al.
        Secondary lymphoid tissue chemokine mediates T cell-dependent antitumor responses in vivo.
        J Immunol. 2000; 164: 4558-4563
        • Gao J.Q.
        • Tsuda Y.
        • Katayama K.
        • Nakayama T.
        • Hatanaka Y.
        • Tani Y.
        • et al.
        Antitumor effect by interleukin-11 receptor alpha-locus chemokine/CCL27, introduced into tumor cells through a recombinant adenovirus vector.
        Cancer Res. 2003; 63: 4420-4425
        • Guiducci C.
        • Di Carlo E.
        • Parenza M.
        • Hitt M.
        • Giovarelli M.
        • Musiani P.
        • et al.
        Intralesional injection of adenovirus encoding CC chemokine ligand 16 inhibits mammary tumor growth and prevents metastatic-induced death after surgical removal of the treated primary tumor.
        J Immunol. 2004; 172: 4026-4036
        • Flanagan K.
        • Glover R.T.
        • Horig H.
        • Yang W.
        • Kaufman H.L.
        Local delivery of recombinant vaccinia virus expressing secondary lymphoid chemokine (SLC) results in a CD4 T-cell dependent antitumor response.
        Vaccine. 2004; 22: 2894-2903
        • Dieu-Nosjean M.C.
        • Massacrier C.
        • Homey B.
        • Vanbervliet B.
        • Pin J.J.
        • Vicari A.
        • et al.
        Macrophage inflammatory protein 3alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors.
        J Exp Med. 2000; 192: 705-718
        • Dieu M.C.
        • Vanbervliet B.
        • Vicari A.
        • Bridon J.M.
        • Oldham E.
        • Ait-Yahia S.
        • et al.
        Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.
        J Exp Med. 1998; 188: 373-386
        • Sallusto F.
        • Schaerli P.
        • Loetscher P.
        • Schaniel C.
        • Lenig D.
        • Mackay C.R.
        • et al.
        Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation.
        Eur J Immunol. 1998; 28: 2760-2769
        • Sozzani S.
        • Allavena P.
        • D’Amico G.
        • Luini W.
        • Bianchi G.
        • Kataura M.
        • et al.
        Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties.
        J Immunol. 1998; 161: 1083-1086
        • Manome Y.
        • Wen P.Y.
        • Hershowitz A.
        • Tanaka T.
        • Rollins B.J.
        • Kufe D.W.
        • et al.
        Monocyte chemoattractant protein-1 (MCP-1) gene transduction: an effective tumor vaccine strategy for non-intracranial tumors.
        Cancer Immunol Immunother. 1995; 41: 227-235
        • Wang H.
        • Nemoto-Sasaki Y.
        • Kondo T.
        • Akiyama M.
        • Mukaida N.
        Potential involvement of monocyte chemoattractant protein (MCP)-1/CCL2 in IL-4-mediated tumor immunity through inducing dendritic cell migration into the draining lymph nodes.
        Int Immunopharmacol. 2003; 3: 627-642
        • Palframan R.T.
        • Jung S.
        • Cheng G.
        • Weninger W.
        • Luo Y.
        • Dorf M.
        • et al.
        Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues.
        J Exp Med. 2001; 194: 1361-1373
        • Gough M.
        • Crittenden M.
        • Thanarajasingam U.
        • Sanchez-Perez L.
        • Thompson J.
        • Jevremovic D.
        • et al.
        Gene therapy to manipulate effector T cell trafficking to tumors for immunotherapy.
        J Immunol. 2005; 174: 5766-5773
        • Clark-Lewis I.
        • Schumacher S.
        • Baggiolini M.
        • Moser B.
        Structure-activity relationships of Interleukin-8 determined using chemically synthesized analogs: critical role of NH2-terminal residues and evidence for uncoupling of neutrophil chemotaxis, exocytosis, and receptor binding activities.
        J Biol Chem. 1991; 266: 23128-23134
        • Hebert C.A.
        • Viytangcol R.V.
        • Baker J.B.
        Scanning mutagenesis of interleukin-8 identifies a cluster of residues required for receptor binding.
        J Biol Chem. 1991; 266: 18989-18994
        • Strieter R.M.
        • Polverini P.J.
        • Kunkel S.L.
        • Arenberg D.A.
        • Burdick M.D.
        • Kasper J.
        • et al.
        The functional role of the ELR motif in CXC chemokine-mediated angiogenesis.
        J Biol Chem. 1995; 270: 27348-27357
        • Okada N.
        • Gao J.Q.
        • Sasaki A.
        • Niwa M.
        • Okada Y.
        • Nakayama T.
        • et al.
        Anti-tumor activity of chemokine is affected by both kinds of tumors and the activation state of the host’s immune system: implications for chemokine-based cancer immunotherapy.
        Biochem Biophys Res Commun. 2004; 317: 68-76
        • Inoue K.
        • Slaton J.W.
        • Eve B.Y.
        • Kim S.J.
        • Perrotte P.
        • Balbay M.D.
        • et al.
        Interleukin 8 expression regulates tumorigenicity and metastases in androgen-independent prostate cancer.
        Clin Cancer Res. 2000; 6: 2104-2119
        • Kitadai Y.
        • Takahashi Y.
        • Haruma K.
        • Naka K.
        • Sumii K.
        • Yokozaki H.
        • et al.
        Transfection of interleukin-8 increases angiogenesis and tumorigenesis of human gastric carcinoma cells in nude mice.
        Br J Cancer. 1999; 81: 647-653
        • Luca M.
        • Huang S.
        • Gershenwald J.E.
        • Singh R.K.
        • Reich R.
        • Bar-Eli M.
        Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis.
        Am J Pathol. 1997; 151: 1105-1113
        • Shi Q.
        • Abbruzzese J.L.
        • Huang S.
        • Fidler I.J.
        • Xiong Q.
        • Xie K.
        Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic.
        Clin Cancer Res. 1999; 5: 3711-3721
        • Hirose K.
        • Hakozaki M.
        • Nyunoya Y.
        • Kobayashi Y.
        • Matsushita K.
        • Takenouchi T.
        • et al.
        Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.
        Br J Cancer. 1995; 72: 708-714
        • Iguchi H.
        • Ono M.
        • Matsushima K.
        • Kuwano M.
        Overproduction of IL-8 results in suppression of bone metastasis by lung cancer cells in vivo.
        Int J Oncol. 2000; 17: 329-333
        • Salcedo R.
        • Ponce M.L.
        • Young H.A.
        • Wasserman K.
        • Ward J.M.
        • Kleinman H.K.
        • et al.
        Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1in angiogenesis and tumor progression.
        Blood. 2000; 96: 34-40
        • Storchova Z.
        • Pellman D.
        From polyploidy to aneuploidy, genome instability and cancer.
        Nat Rev Mol Cell Biol. 2004; 5: 45-54
        • Pollard J.W.
        Tumour-educated macrophages promote tumour progression and metastasis.
        Nat Rev Cancer. 2004; 4: 71-78
        • Leek R.D.
        • Lewis C.E.
        • Whitehouse R.
        • Greenall M.
        • Clarke J.
        • Harris A.L.
        Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma.
        Cancer Res. 1996; 56: 4625-4629
        • Steele R.J.
        • Eremin O.
        • Brown M.
        • Hawkins R.A.
        A high macrophage content in human breast cancer is not associated with favourable prognostic factors.
        Br J Surg. 1984; 71: 456-458
        • Visscher D.W.
        • Tabaczka P.
        • Long D.
        • Crissman J.D.
        Clinicopathologic analysis of macrophage infiltrates in breast carcinoma.
        Pathol Res Pract. 1995; 191: 1133-1139
        • Ueno T.
        • Toi M.
        • Saji H.
        • Muta M.
        • Bando H.
        • Kuroi K.
        • et al.
        Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer.
        Clin Cancer Res. 2000; 6: 3282-3289
        • Valkovic T.
        • Lucin K.
        • Krstulja M.
        • Dobi-Babic R.
        • Jonjic N.
        Expression of monocyte chemotactic protein-1 in human invasive ductal breast cancer.
        Pathol Res Pract. 1998; 194: 335-340
        • Lewis C.E.
        • Leek R.
        • Harris A.
        • McGee J.O.
        Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages.
        J Leukoc Biol. 1995; 57: 747-751
        • Orimo A.
        • Gupta P.B.
        • Sgroi D.C.
        • Arenzana-Seisdedos F.
        • Delaunay T.
        • Naeem R.
        • et al.
        Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion.
        Cell. 2005; 121: 335-348
        • Muller A.
        • Homey B.
        • Soto H.
        • Ge N.
        • Catron D.
        • Buchanan M.E.
        • et al.
        Involvement of chemokine receptors in breast cancer metastasis.
        Nature. 2001; 410: 50-56
        • Jones D.
        • O’Hara C.
        • Kraus M.D.
        • Perez-Atayde A.R.
        • Shahsafaei A.
        • Wu L.
        • et al.
        Expression pattern of T-cell-associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma.
        Blood. 2000; 96: 685-690
        • Hasegawa H.
        • Nomura T.
        • Kohno M.
        • Tateishi N.
        • Suzuki Y.
        • Maeda N.
        • et al.
        Increased chemokine receptor CCR7/EBI1 expression enhances the infiltration of lymphoid organs by adult T-cell leukemia cells.
        Blood. 2000; 95: 30-38
        • Till K.J.
        • Lin K.
        • Zuzel M.
        • Cawley J.C.
        The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes.
        Blood. 2002; 99: 2977-2984
        • Trentin L.
        • Cabrelle A.
        • Facco M.
        • Carollo D.
        • Miorin M.
        • Tosoni A.
        • et al.
        Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas.
        Blood. 2004; 104: 502-508
        • Lopez-Giral S.
        • Quintana N.E.
        • Cabrerizo M.
        • Alfonso-Perez M.
        • Sala-Valdes M.
        • De Soria V.G.
        • et al.
        Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination.
        J Leukoc Biol. 2004; 76: 462-471
        • Zeelenberg I.S.
        • Ruuls-Van Stalle L.
        • Roos E.
        The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases.
        Cancer Res. 2003; 63: 3833-3839
        • Rubin J.B.
        • Kung A.L.
        • Klein R.S.
        • Chan J.A.
        • Sun Y.
        • Schmidt K.
        • et al.
        A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors.
        Proc Natl Acad Sci USA. 2003; 100: 13513-13518
        • Francia di Celle P.
        • Mariani S.
        • Riera L.
        • Stacchini A.
        • Reato G.
        • Foa R.
        Interleukin-8 induces the accumulation of B-cell chronic lymphocytic leukemia cells by prolonging survival in an autocrine fashion.
        Blood. 1996; 87: 4382-4389
        • Abdollahi T.
        • Robertson N.M.
        • Abdollahi A.
        • Litwack G.
        Identification of interleukin 8 as an inhibitor of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in the ovarian carcinoma cell line OVCAR3.
        Cancer Res. 2003; 63: 4521-4526
        • Zhou Y.
        • Larsen P.H.
        • Hao C.
        • Yong V.W.
        CXCR4 is a major chemokine receptor on glioma cells and mediates their survival.
        J Biol Chem. 2002; 17: 49481-49487
        • Marchesi F.
        • Monti P.
        • Leone B.E.
        • Zerbi A.
        • Vecchi A.
        • Piemonti L.
        • et al.
        Increased survival, proliferation, and migration in metastatic human pancreatic tumor cells expressing functional CXCR4.
        Cancer Res. 2004; 64: 8420-8427
        • Burger J.A.
        • Tsukada N.
        • Burger M.
        • Zvaifler N.J.
        • Dell’Aquila M.
        • Kipps T.J.
        Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1.
        Blood. 2000; 96: 2655-2663
        • Hartmann T.N.
        • Burger J.A.
        • Glodek A.
        • Fujii N.
        • Burger M.
        CXCR4 chemokine receptor and integrin signaling co-operate in mediating adhesion and chemoresistance in small cell lung cancer (SCLC) cells.
        Oncogene. 2005; 24: 4462-4471
        • Qiuping Z.
        • Jei X.
        • Youxin J.
        • Wei J.
        • Chun L.
        • Jin W.
        • et al.
        CC chemokine ligand 25 enhances resistance to apoptosis in CD4+ T cells from patients with T-cell lineage acute and chronic lymphocytic leukemia by means of livin activation.
        Cancer Res. 2004; 64: 7579-7587
        • Van Snick J.
        • Houssiau F.
        • Proost P.
        • Van Damme J.
        • Renauld J.C.
        I-309/T cell activation gene-3 chemokine protects murine T cell lymphomas against dexamethasone-induced apoptosis.
        J Immunol. 1996; 157: 2570-2576
        • Ruckes T.
        • Saul D.
        • Van Snick J.
        • Hermine O.
        • Grassmann R.
        Autocrine antiapoptotic stimulation of cultured adult T-cell leukemia cells by overexpression of the chemokine I-309.
        Blood. 2001; 98: 1150-1159
        • Szalai C.
        • Duba J.
        • Prohaszka Z.
        • Kalina A.
        • Szabo T.
        • Nagy B.
        • et al.
        Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp (a) and MCP-1 -2518 G/G genotype in CAD patients.
        Atherosclerosis. 2001; 158: 233-239
        • Valdes A.M.
        • Wolfe M.L.
        • O’Brien E.J.
        • Spurr N.K.
        • Gefter W.
        • Rut A.
        • et al.
        Val64Ile polymorphism in the C–C chemokine receptor 2 is associated with reduced coronary artery calcification.
        Arterioscler Thromb Vasc Biol. 2002; 22: 1924-1928
        • Boring L.
        • Gosling J.
        • Cleary M.
        • Charo I.F.
        Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis.
        Nature. 1998; 394: 894-897
        • Dawson T.C.
        • Kuziel W.A.
        • Osahar T.A.
        • Maeda N.
        Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice.
        Atherosclerosis. 1999; 143: 205-211
        • Gu L.
        • Okada Y.
        • Clinton S.K.
        • Gerard C.
        • Sukhova G.K.
        • Libby P.
        • et al.
        Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.
        Mol Cell. 1998; 2: 275-281
        • Coelho A.
        • Matos A.
        • Catarino R.
        • Pinto D.
        • Pereira D.
        • Lopes C.
        • et al.
        Protective role of the polymorphism CCR2-64I in the progression from squamous intraepithelial lesions to invasive cervical carcinoma.
        Gynecol Oncol. 2005; 96: 760-764
        • Zafiropoulos A.
        • Crikas N.
        • Passam A.M.
        • Spandidos D.A.
        Significant involvement of CCR2-64I and CXCL12-3a in the development of sporadic breast cancer.
        J Med Genet. 2004; 41: e59
        • Rovin B.H.
        • Lu L.
        • Saxena R.
        A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression.
        Biochem Biophys Res Commun. 1999; 259: 344-348
        • Ghilardi G.
        • Biondi M.L.
        • La Torre A.
        • Battaglioli L.
        • Scorza R.
        Breast cancer progression and host polymorphisms in the chemokine system: role of the macrophage chemoattractant protein-1 (MCP-1) -2518 G allele.
        Clin Chem. 2005; 51: 452-455
        • Razmkhah M.
        • Talei A.R.
        • Doroudchi M.
        • Khalili-Azad T.
        • Ghaderi A.
        Stromal cell-derived factor-1 (SDF-1) alleles and susceptibility to breast carcinoma.
        Cancer Lett. 2005; 225: 261-266
        • Razmkhah M.
        • Doroudchi M.
        • Ghayumi S.M.
        • Erfani N.
        • Ghaderi A.
        Stromal cell-derived factor-1 (SDF-1) gene and susceptibility of Iranian patients with lung cancer.
        Lung Cancer. 2005; 49: 311-315
        • de Oliveira Cavassin G.G.
        • De Lucca F.L.
        • Delgado Andre N.
        • Covas D.T.
        • Pelegrinelli Fungaro M.H.
        • Voltarelli J.C.
        • et al.
        Molecular investigation of the stromal cell-derived factor-1 chemokine in lymphoid leukemia and lymphoma patients from Brazil.
        Blood Cells Mol Dis. 2004; 33: 90-93
        • Crittenden M.
        • Gough M.
        • Harrington K.
        • Olivier K.
        • Thompson J.
        • Vile R.G.
        Expression of inflammatory chemokines combined with local tumor destruction enhances tumor regression and long-term immunity.
        Cancer Res. 2003; 63: 5505-5512
        • Zibert A.
        • Balzer S.
        • Souquet M.
        • Quang T.H.
        • Paris-Scholz C.
        • Roskrow M.
        • et al.
        CCL3/MIP-1alpha is a potent immunostimulator when coexpressed with interleukin-2 or granulocyte-macrophage colony-stimulating factor in a leukemia/lymphoma vaccine.
        Hum Gene Ther. 2004; 15: 21-34
        • Giovarelli M.
        • Cappello P.
        • Forni G.
        • Salcedo T.
        • Moore P.A.
        • LeFleur D.W.
        • et al.
        Tumor rejection and immune memory elicited by locally released LEC chemokine are associated with an impressive recruitment of APCs, lymphocytes, and granulocytes.
        J Immunol. 2000; 164: 3200-3206
        • Nakashima E.
        • Oya A.
        • Kubota Y.
        • Kanada N.
        • Matsushita R.
        • Takeda K.
        • et al.
        A candidate for cancer gene therapy: MIP-1 alpha gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice.
        Pharm Res. 1996; 13: 1896-1901
        • van Deventer H.W.
        • Serody J.S.
        • McKinnon K.P.
        • Clements C.
        • Brickey W.J.
        • Ting J.P.
        Transfection of macrophage inflammatory protein 1 alpha into B16 F10 melanoma cells inhibits growth of pulmonary metastases but not subcutaneous tumors.
        J Immunol. 2002; 169: 1634-1639
        • Braun S.E.
        • Chen K.
        • Foster R.G.
        • Kim C.H.
        • Hromas R.
        • Kaplan M.H.
        • et al.
        The CC chemokine CK beta-11/MIP-3 beta/ELC/Exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells.
        J Immunol. 2000; 164: 4025-4031
        • Nomura T.
        • Hasegawa H.
        • Kohno M.
        • Sasaki M.
        • Fujita S.
        Enhancement of anti-tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI-1-ligand chemokine and stromal cell-derived factor-1alpha chemokine genes.
        Int J Cancer. 2001; 91: 597-606
        • Miyata T.
        • Yamamoto S.
        • Sakamoto K.
        • Morishita R.
        • Kaneda Y.
        Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes.
        Cancer Gene Ther. 2001; 8: 852-860
        • Fushimi T.
        • Kojima A.
        • Moore M.A.
        • Crystal R.G.
        Macrophage inflammatory protein 3alpha transgene attracts dendritic cells to established murine tumors and suppresses tumor growth.
        J Clin Invest. 2000; 105: 1383-1393
        • Lavergne E.
        • Combadiere C.
        • Iga M.
        • Boissonnas A.
        • Bonduelle O.
        • Maho M.
        • et al.
        Intratumoral CC chemokine ligand 5 overexpression delays tumor growth and increases tumor cell infiltration.
        J Immunol. 2004; 173: 3755-3762
        • Mule J.J.
        • Custer M.
        • Averbook B.
        • Yang J.C.
        • Weber J.S.
        • Goeddel D.V.
        • et al.
        RANTES secretion by gene-modified tumor cells results in loss of tumorigenicity in vivo: role of immune cell subpopulations.
        Hum Gene Ther. 1996; 7: 1545-1553
        • Hisada M.
        • Yoshimoto T.
        • Kamiya S.
        • Magami Y.
        • Miyaji H.
        • Yoneto T.
        • et al.
        Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT.
        Cancer Gene Ther. 2004; 11: 280-288
        • Yamano T.
        • Kaneda Y.
        • Huang S.
        • Hiramatsu S.H.
        • Hoon D.S.
        Enhancement of immunity by a DNA melanoma vaccine against TRP2 with CCL21 as an adjuvant.
        Mol Ther. 2005;
        • Hu J.Y.
        • Li G.C.
        • Wang W.M.
        • Zhu J.G.
        • Li Y.F.
        • Zhou G.H.
        • et al.
        Transfection of colorectal cancer cells with chemokine MCP-3 (monocyte chemotactic protein-3) gene retards tumor growth and inhibits tumor metastasis.
        World J Gastroenterol. 2002; 8: 1067-1072
        • Wetzel K.
        • Menten P.
        • Opdenakker G.
        • Van Damme J.
        • Grone H.J.
        • Giese N.
        • et al.
        Transduction of human MCP-3 by a parvoviral vector induces leukocyte infiltration and reduces growth of human cervical carcinoma cell xenografts.
        J Gene Med. 2001; 3: 326-337
        • Guo J.
        • Wang B.
        • Zhang M.
        • Chen T.
        • Yu Y.
        • Regulier E.
        • et al.
        Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity.
        Gene Ther. 2002; 9: 793-803
        • Kirk C.J.
        • Hartigan-O’Connor D.
        • Mule J.J.
        The dynamics of the T-cell antitumor response: chemokine-secreting dendritic cells can prime tumor-reactive T cells extranodally.
        Cancer Res. 2001; 61: 8794-8802
        • Vicari A.P.
        • Ait-Yahia S.
        • Chemin K.
        • Mueller A.
        • Zlotnik A.
        • Caux C.
        Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and immunological mechanisms.
        J Immunol. 2000; 165: 1992-2000
        • Ruehlmann J.M.
        • Xiang R.
        • Niethammer A.G.
        • Ba Y.
        • Pertl U.
        • Dolman C.S.
        • et al.
        MIG (CXCL9) chemokine gene therapy combines with antibody-cytokine fusion protein to suppress growth and dissemination of murine colon carcinoma.
        Cancer Res. 2001; 61: 8498-8503
        • Palmer K.
        • Hitt M.
        • Emtage P.C.
        • Gyorffy S.
        • Gauldie J.
        Combined CXC chemokine and interleukin-12 gene transfer enhances antitumor immunity.
        Gene Ther. 2001; 8: 282-290
        • Arenberg D.A.
        • Zlotnick A.
        • Strom S.R.
        • Burdick M.D.
        • Strieter R.M.
        The murine CC chemokine, 6C-kine, inhibits tumor growth and angiogenesis in a human lung cancer SCID mouse model.
        Cancer Immunol Immunother. 2001; 49: 587-592
        • Tanaka T.
        • Manome Y.
        • Wen P.
        • Kufe D.W.
        • Fine H.A.
        Viral vector-mediated transduction of a modified platelet factor 4 cDNA inhibits angiogenesis and tumor growth.
        Nat Med. 1997; 3: 437-442
        • Yamaguchi K.
        • Ogawa K.
        • Katsube T.
        • Shimao K.
        • Konno S.
        • Shimakawa T.
        • et al.
        Platelet factor 4 gene transfection into tumor cells inhibits angiogenesis, tumor growth and metastasis.
        Anticancer Res. 2005; 25: 847-851
        • Addison C.L.
        • Arenberg D.A.
        • Morris S.B.
        • Xue Y.Y.
        • Burdick M.D.
        • Mulligan M.S.
        • et al.
        The CXC chemokine, monokine induced by interferon-gamma, inhibits non-small cell lung carcinoma tumor growth and metastasis.
        Hum Gene Ther. 2000; 11: 247-261
        • Wang Y.Q.
        • Wada A.
        • Ugai S.
        • Tagawa M.
        Expression of the Mig (CXCL9) gene in murine lung carcinoma cells generated angiogenesis-independent antitumor effects.
        Oncol Rep. 2003; 10: 909-913
        • Schwarze S.R.
        • Luo J.
        • Isaacs W.B.
        • Jarrard D.F.
        Modulation of CXCL14 (BRAK) expression in prostate cancer.
        Prostate. 2005; 64: 67-74
        • Cairns C.M.
        • Gordon J.R.
        • Li F.
        • Baca-Estrada M.E.
        • Moyana T.
        • Xiang J.
        Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor.
        J Immunol. 2001; 167: 57-65
        • Bonnotte B.
        • Crittenden M.
        • Larmonier N.
        • Gough M.
        • Vile R.G.
        MIP-3alpha transfection into a rodent tumor cell line increases intratumoral dendritic cell infiltration but enhances (facilitates) tumor growth and decreases immunogenicity.
        J Immunol. 2004; 173: 4929-4935