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

M. A. Rowland-Goldsmith, H. Maruyama, T. Kusama, S. Ralli, Murray Korc

Research output: Contribution to journalArticle

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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 - 2001
Externally publishedYes

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Growth Factor Receptors
Transforming Growth Factors
Pancreatic Neoplasms
Neoplasms
Growth
Clone Cells
In Vitro Techniques
Cell Line
Plasminogen Activator Inhibitor 1
Nude Mice
Protein Isoforms
Adenocarcinoma
Research Design
Amino Acids
Messenger RNA
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Rowland-Goldsmith, M. A.; Maruyama, H.; Kusama, T.; Ralli, S.; Korc, Murray.

In: Clinical Cancer Research, Vol. 7, No. 9, 2001, p. 2931-2940.

Research output: Contribution to journalArticle

Rowland-Goldsmith, M. A. ; Maruyama, H. ; Kusama, T. ; Ralli, S. ; Korc, Murray. / 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. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 9. pp. 2931-2940.
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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.",
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