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

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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 2002
Externally publishedYes

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Pancreatic Neoplasms
Neoplasm Metastasis
Adenocarcinoma
Plasminogen Activator Inhibitor 1
Genes
Neoplasms
Growth
Clone Cells
Plasminogen Activators
Urokinase-Type Plasminogen Activator
Nude Mice
Gene Expression
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Drug Discovery
  • Pharmacology

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.

Soluble type II transforming growth factor-β receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. / Rowland-Goldsmith, Melissa A.; Maruyama, Haruhisa; Matsuda, Kei; Idezawa, Takenao; Ralli, Monica; Ralli, Sonia; Korc, Murray.

In: Molecular Cancer Therapeutics, Vol. 1, No. 3, 01.2002, p. 161-167.

Research output: Contribution to journalArticle

Rowland-Goldsmith, MA, 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, vol. 1, no. 3, pp. 161-167.
Rowland-Goldsmith, Melissa A. ; Maruyama, Haruhisa ; Matsuda, Kei ; Idezawa, Takenao ; Ralli, Monica ; Ralli, Sonia ; Korc, Murray. / Soluble type II transforming growth factor-β receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. In: Molecular Cancer Therapeutics. 2002 ; Vol. 1, No. 3. pp. 161-167.
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