Platelet‐derived growth factor‐B increases colon cancer cell growth in vivo by a paracrine effect

Stephen Hsu, Fei Huang, Eileen Friedman

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

PDGF‐B released from colon tumor cells regulated tumor growth in athymic mice in a paracrine manner by inducing blood vessel formation. A positive correlation was found between expression of PDGF B‐chain in cells grown in vitro and the number of factor VIII‐positive blood vessels in tumors induced by three classes of colon carcinoma cell lines. Elevated expression of PDGF‐B was also correlated with tumor size. Each cell line had the same mutations in the colon cancer genes APC, DCC, and p53 and had wild type c‐K‐ras genes (Huang et al. [1994] Oncogene, 9:3701–3706.) eliminating the possibility that any differences in tumor blood vessel formation were due to mutations and/or deletions in these genes. Colon carcinoma cells released biologically active PDGF capable of stimulating the growth of NIH3T3 cells, which was inhibited by neutralizing antisera to PDGF‐AB chains. An inverse correlation was found between induction of factor VIII‐positive blood vessels and expression of vascular endothelial growth factor (VEGF), while no correlation was seen with expression of either TGFα or k‐FGF. Basic fibroblast growth factor (FGF) expression was not detected in these tumor cells. TGFβ1 was capable of inducing PDGF‐B expression in the undifferentiated U9 colon carcinoma cell line, but this sensitivity was not seen in differentiated cells. In contrast, TGFβ1 inhibited VEGF expression in both undifferentiated cells and differentiated colon cancer cells. Thus, TGFβ1 has two roles in the growth of undifferentiated U9 colon carcinoma cells in vivo: direct stimulation of cell proliferation as we have showed in earlier studies, and an increase in angiogenesis by inducing PDGF‐B. © 1995 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)239-245
Number of pages7
JournalJournal of Cellular Physiology
Volume165
Issue number2
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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