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The effect of antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells.
- Source :
-
Anticancer research [Anticancer Res] 2002 Jan-Feb; Vol. 22 (1A), pp. 103-6. - Publication Year :
- 2002
-
Abstract
- Background: In a previous study we compared the influence of several growth factors on cancer cells in culture and observed that transforming growth factor-beta (TGF-beta) enhanced the invasiveness of several breast cancer cell lines. The objective of the present study was to determine the influence of three unique antiestrogens on TGF-beta-mediated chemotaxis of human breast cancer cells.<br />Materials and Methods: The chemotactic activity of TGF-beta was assayed in vitro using collagen IV-coated transwell chambers with either MCF-7 or MDA-MB-231 human breast cancer cells. The cells were pretreated with antiestrogen for 4 days, harvested and placed in the upper transwell chamber. TGF-beta was added to the lower chamber and cell migration and collagenase release were determined following a 6-hour incubation.<br />Results: In this study TGF-beta enhanced the chemotaxis of both cell types with a much greater effect on the MDA-MB-231 cells. However, TGF-beta-mediated chemotaxis of the MCF-7 cells was inhibited by antiestrogen pretreatment while TGF-beta-mediated chemotaxis of the MDA-MB-231 cells was not altered. Further, neither TGF-beta nor antiestrogen treatment altered collagenase release from either cell line.<br />Conclusion: The data demonstrate that pure antiestrogens are capable of inhibiting TGF-beta-mediated chemotaxis in estrogen receptor (ER)-positive breast cancer cells by a mechanism which is independent of collagenase release. Finally, the results of this study suggest a coupling of the TGF-beta and ER signaling pathways and indicate that TGF-beta may be an important therapeutic target for the treatment or inhibition of breast cancer metastasis.
- Subjects :
- Breast Neoplasms drug therapy
Collagenases metabolism
Estradiol pharmacology
Fulvestrant
Humans
Receptors, Transforming Growth Factor beta biosynthesis
Tamoxifen pharmacology
Transforming Growth Factor beta pharmacology
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Breast Neoplasms pathology
Chemotaxis drug effects
Estradiol analogs & derivatives
Estrogen Receptor Modulators pharmacology
Tamoxifen analogs & derivatives
Transforming Growth Factor beta antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 22
- Issue :
- 1A
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 12017270