Abstract
In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell lines were tumorigenic in both sites. SW1116, SW480 and SW620 did not show local invasive in the NCI-H716 and LS174T cells were both invasive in the caecum, but only NCI-H716 was invasive in the subcutis. HT29 and 5583 (S and E) cells were invasive in the caecum and from that site metastatic to the lungs and/or 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 invasion in vitro (into embryonic chick heart fragments), E-cadherin expression in vivo and in vitro and in vitro production of u-PA and t-PA. These parameters were chosen in view of their purported role in extracellular matrix degradation and intercellular adhesion, which are all involved 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-cadherin expression was observed in vitro together with a relatively high production of u-PA. The non-invasive cell lines showed in vitro homogeneous 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-specific modification of in vivo invasive and metastatic behaviour; (2) invasion in vitro does not correlate with invasion and metastasis in vivo; (3) in vitro non-invasion might be associated with homogeneous E-cadherin expression and low production of u-PA; (4) E-cadherin expression in vitro differs from E-cadherin expression in vivo. The results support the notion that the microenvironment in which cancer cells grow is one of the factors involved in the regulation of invasive and metastatic behaviour.
Highlights
Cell cultureThe following human colorectal cancer cell ines were used: CaCo2 (Fogh et al, 19T7), SW 1116, SW480, SW620 (Leibovitz et al, 1976), NCI-H716 (Park et al, 1987), LS174T (Tom et al, 1976), 5583E, 5583S (Verstijnen et al, 1987) and HT29 (Fogh and Trempe, 1975)
The take rate of human colorectal carcinoma cell lines xenografted in the subcutis of nude mice was 100%, except for CaCo2 cells, which under standard xenografting conditions did not produce tumours (Table I)
Fgu 1 Growth behaviour of colorectal cancer cell lines in vivo. a, Behaviour of SW620 cells in the caecum; the muscularis mucosa is not invaded by tumor cells. b, Behaviour of HT29 cells in the caecum; tumour cells have migrated through the muscularis mucosa, adjacent to crypt cells of the colon. c, Metastatic lesion of 5583S in the liver. d, Metastatic lesion of HT29 in the lung
Summary
The following human colorectal cancer cell ines were used: CaCo2 (Fogh et al, 19T7), SW 1116, SW480, SW620 (Leibovitz et al, 1976), NCI-H716 (Park et al, 1987), LS174T (Tom et al, 1976), 5583E, 5583S (Verstijnen et al, 1987) and HT29 (Fogh and Trempe, 1975). Nude mice under ether anaesthesia were injected with 1 x 106 tumour cells in the subcutis, the spleen or the caecal wall, which was approached through a small median abdominal incision. Two to three days after incubation the coverslips containing the cells were washed briefly in PBS containing Ca2" and Mg2" and fixed in methanol at -25-C for 15mi, air dried and stored at -25-C until use. Fixed cell cultures were taken from frozen stock and brought to room temperature. They were rehydrated in Tris-buffered saline pH 7.6 (TBS) and incubated in 5% bovine serum albumin (BSA) in TBS for 30 min. The slides were incubated with the primary antibody and, after washing with PBS, incubated with rabbit anti-mouse horseradish peroxidase conjugate (Dako, P260, Glostrup, Denmark). Peroxidase activity was visualised with diaminobenzidine and the slides were counterstained with haematoxylin
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