IN-VIVO AND IN-VITRO INVASION IN RELATION TO PHENOTYPIC CHARACTERISTICS OF HUMAN COLORECTAL-CARCINOMA CELLS

In this study we investigated the tumorigenicity, growth pattern and s pontaneous metastatic ability of a series of nine human colorectal car cinoma cell lines after subcutaneous and intracaecal xenografting in n ude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumor igenic in either site; the other cell lines were tumorigenic in both s ites. SW1116, SW480 and SW620 did not show local invasive growth. NCI- H716 and LS174T cells were both invasive in the caecum, but only NCI-H 716 was invasive in the subcutis. HT29 and 5583 (S and E) cells were i nvasive in the caecum and from that site metastatic to the lungs and/o r the liver. HT29 and 5583S cells were both invasive in the subcutis, but 5583E cells were not. Of each category of in vivo behaviour in the caecum, one cell line was further investigated with regard to invasio n in vitro (into embryonic chick heart fragments), E-cadherin expressi on in vivo and in vitro and in vitro production of u-PA and t-PA. Thes e parameters were chosen in view of their purported role in extracellu lar matrix degradation and intercellular adhesion, which are all invol ved in the invasive and metastatic cascade. Invasion in vitro was not predictive for invasion or metastasis in vivo. In the cell line which showed invasion in embryonic chick heart tissue, heterogeneous E-cadhe rin expression was observed in vitro together with a relatively high p roduction of u-PA. The non-invasive cell lines showed in vitro homogen eous expression of E-cadherin with a relatively low production of u-PA . In vivo expression of E-cadherin was either absent or heterogeneous. We conclude that: (1) colorectal carcinoma xenografts show site-speci fic modification of in vivo invasive and metastatic behaviour; (2) inv asion in vitro does not correlate with invasion and metastasis in vivo ; (3) in vitro non-invasion might be associated with homogeneous E-cad herin expression and low production of u-PA; (4) E-cadherin expression in vitro differs from E-cadherin expression in vivo. The results supp ort the notion that the microenvironment in which cancer cells grow is one of the factors involved in the regulation of invasive and metasta tic behaviour.