Estrogens and antiestrogens stimulate release of bone resorbing activity by cultured human breast cancer cells

A. Valentin-Opran, G. Eilon, S. Saez, G. R. Mundy

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38 Scopus citations

Abstract

Patients with advanced breast cancer may develop acute, severe hypercalcemia when treated with estrogens or antiestrogens. In this study, we examined the effects of estrogens and related compounds on the release of bone resorbing activity by cultured human breast cancer cells in vitro. We found that the estrogen receptor positive breast cancer cell line MCF-7 releases bone resorbing activity in response to low concentrations of 17β-estradiol. Bone resorbing activity was also released in response to the antiestrogen nafoxidine. Other steroidal compounds has no effect on the release of bone resorbing activity. Estrogen-stimulated release of bone resorbing activity occurred with live bone cultures, but not with devitalized bones, indicating that the effect was bone cell mediated. The breast cancer cell line MDA-231, which does not have estrogen receptors, did not release bone resorbing activity in response to 17β-estradiol or nafoxidine. Release of the bone resorbing activity by MCF-7 cells incubated with 17β-estradiol was inhibited by indomethacin (10 μM) and flufenamic acid (50 μM), two structurally unrelated compounds that inhibit prostaglandin synthesis. Concentrations of 17β-estradiol and nafoxidine that caused increased release of bone resorbing activity by the breast cancer cells caused a 4- to 5-fold increase in release of prostaglandins of the E series by MCF-7 cells. These data may explain why some patients with advanced breast cancer develop acute hypercalcemia when treated with estrogens or antiestrogens, and why bone metastases are more common in patients with estrogen receptor positive tumors.

Original languageEnglish (US)
Pages (from-to)726-731
Number of pages6
JournalJournal of Clinical Investigation
Volume75
Issue number2
DOIs
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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