Secretion of extracellular matrix (fibronectin), growth factor (transforming growth factor beta) and protease (cathepsin D) by hepatoma cells

We investigated facilitation of invasion by growth factors and chemotactic factors in tumor cell lines, particularly hepatocellular carcinoma. Hepatom a cells (PLC/PRF/5 and Hep G2) showed strong chemotaxis toward their respec tive conditioned media while metastatic pancreatic cancer cells (SU.86.86) and colon cancer cells (LS 174T) did not migrate toward their respective co nditioned media. Based on immunoblotting, PLC/PRF/5 cells secrete fibronect in (an extracellular matrix constituent), transforming growth factor-beta ( TGF beta; a growth factor), and cathepsin D (a protease). Fibronectin induc ed a migratory response in PLC/PRF/5 cells, and anti-fibronectin antibody a bolished the migratory response of these cells to their conditioned medium, Anti-integrin-beta(1) antibody also impeded migration of these cells towar d conditioned medium. Polyclonal anti-TGF beta antibody and protease inhibi tors (alpha(2)-macroglobulin and leupeptin) added to culture media-modulate d secretion of fibronectin by PLC/PRF/5 cells. Although exogenous TGF beta suppressed SU.86.86 cells, it enhanced PLC/PRF/5 cell adhesion to substrate , increasing viable cell numbers. These actions indicate that hepatocellula r carcinoma may possess a forceful autocrine mechanism enabling cells to su rvive and proliferate under cirrhotic conditions. Copyright (C) 2000 S. Kar ger AG, Basel.