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. Hepatoma cells (PLC/PRF/5 and Hep G2) showed strong chemotaxis toward their respective conditioned media while metastatic pancreatic cancer cells (SU.86.86) and colon cancer cells (LS 174T) did not migrate toward their respective conditioned media. Based on immunoblotting, PLC/PRF/5 cells secrete fibronectin (an extracellular matrix constituent), transforming growth factor-beta (TGFbeta; a growth factor), and cathepsin D (a protease). Fibronectin induced a migratory response in PLC/PRF/5 cells, and anti-fibronectin antibody abolished the migratory response of these cells to their conditioned medium. Anti-integrin-beta(1) antibody also impeded migration of these cells toward conditioned medium. Polyclonal anti-TGFbeta antibody and protease inhibitors (alpha(2)-macroglobulin and leupeptin) added to culture media-modulated secretion of fibronectin by PLC/PRF/5 cells. Although exogenous TGFbeta suppressed SU.86.86 cells, it enhanced PLC/PRF/5 cell adhesion to substrate, increasing viable cell numbers. These actions indicate that hepatocellular carcinoma may possess a forceful autocrine mechanism enabling cells to survive and proliferate under cirrhotic conditions.
Ito
H
H
First Department of Surgery, School of Medicine, Chiba University, Japan. ito@med.m.chiba-u.ac.jp
Miyazaki
M
M
Nishimura
F
F
Nakajima
N
N
D000912:Antibodies, Neoplasm / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002402:Cathepsin D / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division; D002633:Chemotaxis; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D005353:Fibronectins; D011480:Protease Inhibitors; D016212:Transforming Growth Factor beta; D002402:Cathepsin D