Modulation of fibronectin expression and proteolytic activity associated with the invasive and metastatic phenotype in two new murine mammary tumor cell lines.

Two cell lines obtained by sequential subcultures from primary cultures of the murine mammary adenocarcinomas M3 and MM3 were characterized. During LM3 cell line evolution an increase in the anchorage-independent growth ability, a displacement towards a triploid level in the chromosomic distribution and a loss of fibronectin (FN) expression were observed. LMM3 cell line showed a tetraploid chromosomic number and was unable to produce FN, behaving in a similar way as its parental tumor MM3. The local invasive ability as well as the spontaneous metastatic capacity of LM3 cells inoculated subcutaneously (s.c.) increased with the passage number and were associated with the progressive loss of FN expression as well as to the appearence of membrane bound uPA. LMM3 cells, which did not express FN, maintained the high spontaneous metastasic capacity already shown by the parental tumor MM3 but acquired a higher local invasive phenotype.