Soluble type II transforming growth factor-β (TGF-β) receptor inhibits TGF-β signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation

Melissa A. Rowland-Goldsmith, Haruhisa Maruyama, Toshiyuki Kusama, Sonia Ralli, Murray Korc

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Human pancreatic ductal adenocarcinomas overexpress transforming growth factor-βs (TGF-βs). This overexpression has been correlated with decreased patient survival. TGF-βs bind to a type II TGF-β receptor (TβRII) dimer, which heterotetramerizes with a type I TGF-β receptor (TβRI) dimer, thereby activating downstream signaling. Purpose and Experimental Design: To determine whether blocking TGF-β actions would suppress pancreatic cancer cell growth in vivo, we expressed a soluble TβRII, encoding amino acids 1-159 of the extracellular domain in COLO-357 human pancreatic cancer cells. This cell line expresses all of the three mammalian TGF-β isoforms and is growth inhibited by TGF-β in vitro. Results: COLO-357 clones expressing soluble TβRII were no longer growth inhibited by exogenous TGF-β1 and exhibited a marked decrease in their invasive capacity in vitro. When injected s.c. into athymic mice, these clones exhibited attenuated growth rates and angiogenesis and decreased levels of plasminogen activator inhibitor-1 mRNA as compared with tumors formed by sham-transfected cells. Conclusions: These results indicate that endogenous TGF-βs can confer a growth advantage in vivo to a pancreatic cancer cell line that is growth inhibited in vitro and suggest that a soluble receptor approach can be used to block these tumorigenic effects of TGF-βs.

Original languageEnglish (US)
Pages (from-to)2931-2940
Number of pages10
JournalClinical Cancer Research
Volume7
Issue number9
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Soluble type II transforming growth factor-β (TGF-β) receptor inhibits TGF-β signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation'. Together they form a unique fingerprint.

  • Cite this