Abstract
Proteolytic enzymes play a complex role in tumour growth and invasion. To explore
the impact of tumour stroma on invasiveness and expression of proteolytic enzymes,
we used a xenograft mouse model where tumours in tongue and skin were established
from various human cancer cell lines. Gelatinolytic activity in the tumours was investigated
by a novel in situ zymography technique which enables high image resolution. In vivo and in vitro expression of various proteolytic enzymes were analysed at transcriptional and protein
level using RT-qPCR, immunohistochemistry and SDS–PAGE substrate zymography. At the
mRNA level all cell lines were found to express MMP-2, -7, -14, uPA and uPAR. In addition,
two out of three cell lines expressed MMP-9. Histological analyses revealed that tongue
tumours had an invasive growth pattern, associated with reduced E-cadherin expression.
In contrast, the skin tumours established from the same cell lines were non-invasive.
Tongue tumours of all cell lines showed strong gelatinolytic activity especially at
the invasive front, which was not seen in the non-invasive skin tumours. Our results
show a close relationship between tumour invasiveness and gelatinolytic activity at
the tumour front. Furthermore, in our model, both invasiveness and activity of tumour-associated
proteolytic enzymes were more dependent on the tumour microenvironment than on inherent
properties of the cancer cells.
Keywords
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Article info
Publication history
Published online: October 08, 2010
Accepted:
September 2,
2010
Received in revised form:
August 19,
2010
Received:
June 25,
2010
Footnotes
☆The Norwegian Cancer Society, The Erna and Olav Aakre Foundation for Cancer Research and The North Norwegian Health Authorities.
Identification
Copyright
© 2010 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
