Soluble type II transforming growth factor-β receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis

Melissa A. Rowland-Goldsmith, Haruhisa Maruyama, Kei Matsuda, Takenao Idezawa, Monica Ralli, Sonia Ralli, Murray Korc

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-βs (TGF-βs). To determine whether TGF-βs can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-β receptor (sTβRII) that blocks cellular responsiveness to TGF-β1. When injected s.c. in athymic mice, PANC-1 clones expressing sTβRII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-βs act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sTβRII may ultimately have a therapeutic benefit in PDAC.

Original languageEnglish (US)
Pages (from-to)161-167
Number of pages7
JournalMolecular cancer therapeutics
Volume1
Issue number3
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Soluble type II transforming growth factor-β receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis'. Together they form a unique fingerprint.

  • Cite this

    Rowland-Goldsmith, M. A., Maruyama, H., Matsuda, K., Idezawa, T., Ralli, M., Ralli, S., & Korc, M. (2002). Soluble type II transforming growth factor-β receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. Molecular cancer therapeutics, 1(3), 161-167.