Transforming growth factor‐beta inhibits proliferation of human ovarian cancer cells obtained from ascites

Jean Hurteau, Gustavo C. Rodriguez, Regina S. Whitaker, Shafquat Shah, Gordon Mills, Robert C. Bast, Andrew Berchuck

Research output: Contribution to journalArticle

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Abstract

Background. Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor‐β and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth‐inhibited by or produce transforming growth factor‐β. Methods. Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti‐CD45 antibody. The effect of transforming growth factor‐β on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor‐β1 and β2 also was performed in these cells. Results. Transforming growth factor‐β (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95%) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28% of control values. In addition, there was no difference in dosedependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61%) were found to express immunohistochemically detectable transforming growth factor‐β, but immunostaining was not observed in 39% of cases. Conclusions. Although most primary ovarian cancer cells remain sensitive to the growth‐inhibitory effect of transforming growth factor‐β, loss of production may interrupt the transforming growth factor‐β autocrine inhibitory loop and play a role in the development of some ovarian cancers.

Original languageEnglish (US)
Pages (from-to)93-99
Number of pages7
JournalCancer
Volume74
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Ascites
Transforming Growth Factors
Ovarian Neoplasms
Growth
Thymidine
Density Gradient Centrifugation
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Staining and Labeling
Cell Line
Antibodies

Keywords

  • growth factor
  • growth inhibition
  • ovarian cancer
  • transforming growth factor‐β

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Transforming growth factor‐beta inhibits proliferation of human ovarian cancer cells obtained from ascites. / Hurteau, Jean; Rodriguez, Gustavo C.; Whitaker, Regina S.; Shah, Shafquat; Mills, Gordon; Bast, Robert C.; Berchuck, Andrew.

In: Cancer, Vol. 74, No. 1, 01.01.1994, p. 93-99.

Research output: Contribution to journalArticle

Hurteau, Jean ; Rodriguez, Gustavo C. ; Whitaker, Regina S. ; Shah, Shafquat ; Mills, Gordon ; Bast, Robert C. ; Berchuck, Andrew. / Transforming growth factor‐beta inhibits proliferation of human ovarian cancer cells obtained from ascites. In: Cancer. 1994 ; Vol. 74, No. 1. pp. 93-99.
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abstract = "Background. Previously, the authors found that immortalized ovarian cancer cell lines generally were resistant to the growth inhibitory effect of transforming growth factor‐β and frequently had lost the ability to produce or activate this growth factor. In this study, the authors examined whether early passage epithelial ovarian cancer cells obtained from ascites are growth‐inhibited by or produce transforming growth factor‐β. Methods. Ovarian cancer cells were purified from ascites by percoll gradient density centrifugation, and inflammatory cells were removed using anti‐CD45 antibody. The effect of transforming growth factor‐β on the proliferation of ovarian cancer cells was assessed using the thymidine incorporation assay. Immunohistochemical staining for transforming growth factor‐β1 and β2 also was performed in these cells. Results. Transforming growth factor‐β (10 ng/ml) significantly inhibited [3H]thymidine incorporation in 19 of 20 (95{\%}) primary ovarian cancers (P < 0.05). In cases in which significant inhibition was seen, the mean thymidine incorporation was 33 plus or minus 28{\%} of control values. In addition, there was no difference in dosedependent inhibition of proliferation between ovarian cancer cells and normal ovarian epithelial cells. Eleven of 18 ovarian cancers (61{\%}) were found to express immunohistochemically detectable transforming growth factor‐β, but immunostaining was not observed in 39{\%} of cases. Conclusions. Although most primary ovarian cancer cells remain sensitive to the growth‐inhibitory effect of transforming growth factor‐β, loss of production may interrupt the transforming growth factor‐β autocrine inhibitory loop and play a role in the development of some ovarian cancers.",
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