Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions

David H. Berger, Christine A. O'Mahony, Hongmiao Sheng, Jinyi Shao, Daniel Albo, Raymond N. DuBois, R. Daniel Beauchamp

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background. An alteration in the expression of and response to transforming growth factor-beta 1 (TGF-β1) appears to be an important event during colorectal carcinogenesis. However, the precise role of TGF-β1 in colorectal carcinogenesis is not clear. We have previously described in detail the changes in cell proliferation and differentiation caused by chronic exposure to TGF-β1. In this study we sought to better characterize the changes in tumor cell-cell matrix interactions seen during TGF-β1-mediated intestinal transformation. Methods. Rat intestinal epithelial cells (RIE) and RIE cells transformed by chroinic exposure to TGF-β1 (RIE-Tr) were treated with TGF-β1 and production of components of the plasmin/plasminogen system measured by ELISA and Western blotting. TGF-β1 effects on invasion and adhesion were determined in vitro. The role of urokinase on TGF-β1-mediated invasion and adhesion were determined using immunoneutralization. The role of COX-2 was determined suing a specific COS-2 inhibitor. Results. TGF-β1 had no effect on RIE-1 adhesion to collagen types I and IV, fibronectin, and laminin, or invasion through collagen types I and IV. However, 5 ng/mL TGF-β1 significantly increased the invasiveness and decreased the adhesiveness of RIE-Tr. This effect of TGF-β1 on RIE-Tr was associated with a significant increase in plasmin activity secondary to increased expression of uPA. TGF-β1 had no effect on either uPA receptor or PAI-1 in this system. Antibodies to uPA completely blocked the TGF-β1-mediated invasiveness of the RIE-Tr cells and returned their adhesiveness to basement membrane proteins to baseline. Addition of the selective Cox-2 inhibitor SC-58125 resulted in a dose-dependent decrease in TGF-β1-mediated invasion and uPA expression. Conclusion. This study provides additional evidence for TGF-β1 as a tumor promoter during intestinal carcinogenesis and a possible new mechanism for Cox-2-related colon carcinogenesis.

Original languageEnglish (US)
Pages (from-to)568-579
Number of pages12
JournalSurgery
Volume133
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

Fingerprint

Cell Communication
Transforming Growth Factor beta
Neoplasms
Epithelial Cells
Carcinogenesis
Adhesiveness
Collagen Type IV
Fibrinolysin
Collagen Type I
Plasminogen
Plasminogen Activator Inhibitor 1
Urokinase-Type Plasminogen Activator
Laminin
Fibronectins
Basement Membrane
Cell Adhesion
Carcinogens
Cell Differentiation
Membrane Proteins
Colon

ASJC Scopus subject areas

  • Surgery

Cite this

Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions. / Berger, David H.; O'Mahony, Christine A.; Sheng, Hongmiao; Shao, Jinyi; Albo, Daniel; DuBois, Raymond N.; Beauchamp, R. Daniel.

In: Surgery, Vol. 133, No. 5, 01.05.2003, p. 568-579.

Research output: Contribution to journalArticle

Berger, David H. ; O'Mahony, Christine A. ; Sheng, Hongmiao ; Shao, Jinyi ; Albo, Daniel ; DuBois, Raymond N. ; Beauchamp, R. Daniel. / Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions. In: Surgery. 2003 ; Vol. 133, No. 5. pp. 568-579.
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AU - Albo, Daniel

AU - DuBois, Raymond N.

AU - Beauchamp, R. Daniel

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AB - Background. An alteration in the expression of and response to transforming growth factor-beta 1 (TGF-β1) appears to be an important event during colorectal carcinogenesis. However, the precise role of TGF-β1 in colorectal carcinogenesis is not clear. We have previously described in detail the changes in cell proliferation and differentiation caused by chronic exposure to TGF-β1. In this study we sought to better characterize the changes in tumor cell-cell matrix interactions seen during TGF-β1-mediated intestinal transformation. Methods. Rat intestinal epithelial cells (RIE) and RIE cells transformed by chroinic exposure to TGF-β1 (RIE-Tr) were treated with TGF-β1 and production of components of the plasmin/plasminogen system measured by ELISA and Western blotting. TGF-β1 effects on invasion and adhesion were determined in vitro. The role of urokinase on TGF-β1-mediated invasion and adhesion were determined using immunoneutralization. The role of COX-2 was determined suing a specific COS-2 inhibitor. Results. TGF-β1 had no effect on RIE-1 adhesion to collagen types I and IV, fibronectin, and laminin, or invasion through collagen types I and IV. However, 5 ng/mL TGF-β1 significantly increased the invasiveness and decreased the adhesiveness of RIE-Tr. This effect of TGF-β1 on RIE-Tr was associated with a significant increase in plasmin activity secondary to increased expression of uPA. TGF-β1 had no effect on either uPA receptor or PAI-1 in this system. Antibodies to uPA completely blocked the TGF-β1-mediated invasiveness of the RIE-Tr cells and returned their adhesiveness to basement membrane proteins to baseline. Addition of the selective Cox-2 inhibitor SC-58125 resulted in a dose-dependent decrease in TGF-β1-mediated invasion and uPA expression. Conclusion. This study provides additional evidence for TGF-β1 as a tumor promoter during intestinal carcinogenesis and a possible new mechanism for Cox-2-related colon carcinogenesis.

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