Growth-factor-independence and invasive properties of colorectal carcinoma cells

✍ Scribed by Noel N. Williams; Tibor Györfi; Dimitrios Iliopoulos; Dorothee Herlyn; David Greenstein; Alban J. Linnenbach; John M. Daly; Pamela Jensen; Ulrich Rodeck; Meenhard Herlyn

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: French
• Weight: 832 KB
• Volume: 50
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910500218

✦ Synopsis

Abstract

During serial passage of the colorectal carcinoma cell line SW1116 in athymic nude mice, we selected 2 variants that metastasized to the lungs and liver. The metastatic capacity of these in vivo variant cell lines was associated with their ability to (1) grow under growth‐factor‐deprived conditions, (2) invade and transgress a reconstructed basement membrane with high effectiveness, and (3) produce higher activities of the substrate‐ degrading enzymes collagenase and plasminogen activator as compared to parental cells. To assess the relative contribution of growth‐factor‐independence and high levels of invasiveness/motility to the metastatic phenotype, variants of 6 colorectal carcinomas were selected in vitro by adaptation to a growth‐factor‐free culture medium followed by selection of highly invasive cells in chemoinvasion assays. Four out of 6 cell lines selected for growth‐factor‐independence showed significantly higher levels of invasiveness through reconstructed membranes, suggesting co‐segregation of growth‐factor‐independence and high levels of invasiveness in vitro. Using an in vitro chemoinvasion assay, 2 poorly and I highly invasive cell line were further selected for invasiveness. After 6 selection passages, all cell lines were highly invasive and showed high motility rates. However, when injected s.c. into athymic nude mice to test their metastatic capacity in vivo, double‐selected variant cell lines did not form spontaneous metastases. Our results indicate that growth‐factor‐independence and high levels of invasiveness, although associated with the metastatic phenotype, are not sufficient for experimental metastasis formation of colorectal carcinoma cells in vivo.