Growth-factor-independence and invasive properties of colorectal carcinoma cells.
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 1 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.
Williams
N N
NN
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Györfi
T
T
Iliopoulos
D
D
Herlyn
D
D
Greenstein
D
D
Linnenbach
A J
AJ
Daly
J M
JM
Jensen
P
P
Rodeck
U
U
Herlyn
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015179:Colorectal Neoplasms / Q000473:pathology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D009368:Neoplasm Transplantation; D010641:Phenotype; D014407:Tumor Cells, Cultured
D006133:Growth Substances