Abstract | BACKGROUND: PURPOSE: The purpose of our study was to determine whether transferrin may reverse the inhibitory action of suramin on metastatic prostate-derived cell lines. METHODS: RESULTS: The results clearly demonstrate that the androgen-insensitive metastatic cell lines (PC-3, PC-3M, DU-145, and TSU-Pr1) demonstrate increased cell numbers when exposed to holotransferrin or apotransferrin, while the androgen-sensitive cell line (LNCaP) did not show any increase. All cell lines demonstrated a similar number of transferrin receptors and transferrin receptor mRNA. We used these maximally inhibitory, but clinically relevant, concentrations of suramin to determine whether transferrin could reverse the inhibition, and it did, but only in the androgen-insensitive metastatic lines. Indeed, in the PC-3 cells, inhibition turned to stimulation with the addition of transferrin, and even at the highest concentration of suramin tested, 400 microM, a concentration that would be toxic to patients, the amount of inhibition by suramin was still reduced by more than 50% by transferrin in TSU-Pr1 cells. In the androgen-sensitive LNCaP cells, however, transferrin had limited ability to block the inhibitory activity of suramin. CONCLUSIONS: Concentrations of tumor-stimulating factors, such as transferrin, in the metastatic microenvironment need to be taken into consideration in the use of suramin and suramin-like derivatives. Novel strategies need to be identified that will negate the action of transferrin on androgen-insensitive cells.
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Authors | S M Donat, C T Powell, R S Israeli, W R Fair, W D Heston |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 87
Issue 1
Pg. 41-6
(Jan 04 1995)
ISSN: 0027-8874 [Print] United States |
PMID | 7666462
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Androgens
- Apoproteins
- RNA, Messenger
- Receptors, Transferrin
- Transferrin
- apotransferrin
- Suramin
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Topics |
- Androgens
(physiology)
- Apoproteins
(pharmacology)
- Humans
- Male
- Prostatic Neoplasms
(drug therapy, physiopathology, ultrastructure)
- RNA, Messenger
(analysis)
- Receptors, Transferrin
(analysis, genetics)
- Suramin
(antagonists & inhibitors)
- Transferrin
(pharmacology)
- Tumor Cells, Cultured
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