Soluble and matrix-associated heparan sulfate proteoglycans increase expression of erb-B2 and erb-B3 in colon cancer cell lines.
We investigated the effect of hepatocyte-derived extracellular matrix (ECM) on the expression of erb-B2 and erb-B3 in colon cancer cell lines, as well as the role of erb-B2 and erb-B3 in colon cancer cell proliferation. Colon cancer cell lines plated on hepatocyte-derived ECM had increased protein levels of both erb-B2 and erb-B3. The addition of soluble recombinant proteoglycan syndecan-4 also resulted in higher expression of erb-B2 and erb-B3. We prepared hepatocyte-derived ECM from 1 to 7 days' cultures of hepatocytes, which contained different amounts of sulfated glycosaminoglycans. There was a direct correlation between the amounts of sulfated glycosaminoglycans in the ECM and the levels of erb-B2 and erb-B3 in the colon cell line KM12. The stimulatory effect of hepatocyte-derived ECM was abolished when the colon cancer cells were cultured in the presence of antibodies to erb-B2. These studies show that hepatocyte-derived ECM and the heparan sulfate proteoglycans present in it are responsible for inducing erb-B2 and erb-B3 in colon cancer cells. The growth stimulatory effect of extracellular matrix is mediated, at least in part, by increased expression of erb-B2 and erb-B3.
Zvibel
I
I
Liver Metastasis Research Group, Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. isab@tasmc.health.gov.il
Brill
S
S
Halpern
Z
Z
Moskovitz
S
S
Yayon
A
A
Papa
M
M
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D053671:Syndecan-4; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000911:Antibodies, Monoclonal; D019812:Heparan Sulfate Proteoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D053671:Syndecan-4; C508304:SDC4 protein, human