Abstract
Human tumour cell lines have played an important part in our understanding of cancer
and have been used extensively in the discovery and characterisation of new chemotherapeutic
drugs. A potential weakness of such cell lines is that they may have lost important
properties originally possessed in vivo, including potential targets for therapy. This review discusses how possible differences
between tumour cells in cancer patients and cell lines might be identified by the
use of short-term cultures of human tumour cells taken directly from cancer tissue,
termed here primary cultures. Cell-cycle time is one important difference between
tumours and cell lines and it is known that the cell-cycle times of primary cultures
cover the same wide range as estimated in vivo cell-cycle times. Because tumour cells have at least two pathways to cell death,
one from interphase and one from mitosis, changes in cell-cycle length can modify
the balance of such pathways. Responses of primary cultures to DNA-damaging drugs
and inhibitors of growth factor receptors also differ from those of cell lines, suggesting
that the process of developing a cell line can result in the loss of important cellular
responses. Without an appreciation of these changes our ability to discover new targets
for the development of improved cancer therapy may be jeopardised. The identification
of cell lines that preserve potential targets is an important goal in cancer biology
and research using primary cultures will help in this identification.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Current results of the screening program at the Division of Cancer Treatment, National Cancer Institute.European Journal of Cancer. 1981; 17: 129-142
- A semiautomated microculture method for investigating growth inhibitory effects of cytotoxic compounds on exponentially growing carcinoma cells.Analytical Biochemistry. 1984; 139: 272-277
- Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen.Drug Development Research. 1995; 34: 91-109
Holbeck S. Update on NCI in vitro drug screen utilities. European Journal of Cancer 2003, in press.
- The epidermal growth factor receptor family of tyrosine kinases and cancer.Current Medicinal Chemistry. 1996; 3: 211-226
- A method to measure the duration of DNA synthesis and the potential doubling time from a single sample.Cytometry. 1985; 6: 620-626
- Measurement of cell kinetics in human tumours in vivo using bromodeoxyuridine incorporation and flow cytometry.British Journal of Cancer. 1988; 58: 423-431
- Short-term cultures of clinical tumor material.Oncology Research. 1999; 11: 115-124
- The p21(Cip1) and p27(Kip1) CDK ‘inhibitors’ are essential activators of cyclin D-dependent kinases in murine fibroblasts.EMBO Journal. 1999; 18: 1571-1583
- Microculture-based chemosensitivity testing.Journal of the National Cancer Institute. 1992; 84: 340-345
- Cultures of surgical material from lung cancers.in: Driscoll B. Lung Cancer. Humana Press, Inc, Totowa, New Jersey2002: 527-544
- Resistance mechanisms determining the in vitro sensitivity to paclitaxel of tumour cells cultured from patients with ovarian cancer.European Journal of Cancer. 1995; 31A: 230-237
- A mathematical model for the analysis of the cell cycle in cell lines derived from human tumors.Journal of Mathematical Biology. 2003; 47: 295-312
- Primary bioassay of human tumor stem cells.Science. 1977; 197: 461-463
- Growth of human tumour cell colonies from biopsies using two soft-agar techniques.British Journal of Cancer. 1978; 38: 77-81
- Human tumour cloning assays.Cancer Metastasis Reviews. 1988; 7: 357-371
- Dysregulation of apoptosis in cancer.Journal of Clinical Oncology. 1999; 17: 2941-2953
- Different mechanisms between premitotic apoptosis and postmitotic apoptosis in X-irradiated U937 cells.International Journal of Radiation Oncology Biology and Physics. 2000; 47: 767-777
- Mitotic block induced in HeLa cells by low concentrations of paclitaxel (taxol) results in abnormal mitotic exit and apoptotic cell death.Cancer Research. 1996; 56: 816-825
Basse B, Baguley BC, Marshall ES, et al. Modelling cell death in human tumour cell lines exposed to the anticancer drug paclitaxel. Journal of Mathematical Biology 2003, in press.
- Mitotic death.Cancer Cell International. 2001; 1: 1
- Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function.Cancer Research. 1984; 44: 1693-1697
- Short term culture of ovarian cancer cells.in: Mok J.E. Ninth Biennial Meeting of the International Gynecologic Cancer Society. Monduzzi Editore, Bologna2002: 173-176
- Targeting epidermal growth factor receptor-are we missing the mark?.Lancet. 2003; 362: 62-64
- Targeting the epidermal growth factor receptor in cancer.Cancer Research. 2003; 63: 1-5
- Inhibition of growth of primary human tumour cell cultures by a 4-anilinoquinazoline inhibitor of the epidermal growth factor receptor family of tyrosine kinases.European Journal of Cancer. 1998; 34: 1086-1090
- Tyrosine kinase inhibitors. 18. 6-Substituted 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as soluble, irreversible inhibitors of the epidermal growth factor receptor.Journal of Medicinal Chemistry. 2001; 44: 429-440
- Tyrosine kinase inhibitors. 8. An unusually steep structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a potent inhibitor of the epidermal growth factor receptor.Journal of Medicinal Chemistry. 1996; 39: 267-276
- A gene expression database for the molecular pharmacology of cancer.Nature Genetics. 2000; 24: 236-244
- Tumour growth dynamics.British Medical Bulletin. 1991; 47: 47-63
Article info
Publication history
Accepted:
December 23,
2003
Received in revised form:
December 2,
2003
Received:
September 30,
2003
Identification
Copyright
© 2004 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.