Experimental models of invasion and metastasis; can they provide reliable answers for the role of proteases in cancer?
This paper discusses the feasibility of extrapolating to human cancer results obtained concerning the role of proteases in experimental models of invasion and metastasis. It is customary to view metastasis as a series of individual steps, which must be completed in sequence for the process to be successful. The role of proteases in this process is usually studied by testing the blocking effects of various inhibitors on tumor cell invasion of extracellular matrices (ECM), or in assays of "experimental metastasis" (tail vein injections). The tests of invasion, which utilize established tumor cell lines, provide an account of the type of proteases that potentially may be produced by cancer cells, but, as indicated by recent evidence, they do not reflect the much more restricted repertoire of proteases detected by in situ techniques in human cancer cells. It is much more difficult to find in the progression of human cancer the counterpart to the widely used tail vein injection, which purports to test "late" stages of metastasis, since intravasation is most likely a slow, selective process and not a massive flux of a huge number of cells injected under substantial pressure resulting in non-physiological responses. As a rule, therefore, once it is established that an isolated cancer cell can produce a protease, or degrade and invade ECM, the question is whether this process actually occurs according to a model most reflective of the disease studied (such as orthotopic models) and whether this activity is actually present in cancer tissue sections.
Ossowski
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Department of Medicine, Rochelle Belfer Chemotherapy Foundation Laboratory, Mount Sinai School of Medicine, New York, NY 10026, USA.
D000818:Animals; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*
D010450:Endopeptidases