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Breast Cancer Stimulation of Osteolysis

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Annual rept. 1 Sep 97-31 Aug 98

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Breast cancer metastasis to bone results in the loss of significant amounts of bone tissue through increased osteoclast activity. The purpose of this research is to determine what growth factors are secreted by tumors and how they influence osteoclasts. We have determined the tumors make IGF-I, IGF-II, M-CSF, PTHrP, TGF-Beta, and TNF-alpha. We are examining the effects of these growth factors on bone resorption and survival of avian osteoclasts and mouse osteoclast-like cells in vitro. We observe a similar stimulation of resorption activity by these factors between the two cell types. We have also observed a decrease in cell death with breast cancer cell conditioned media treatment which appears to be the result of TGF-Beta andor TNF-alpha treatment There are differences in the effects of the growth factors on attachment of the cells as IGF-I, IGF-II, PTHrP, and TNF-alpha all stimulate increased attachment of the mouse cells while having no effect on avian cell attachment. We are currently exploring whether this is due to differences in the state of differentiation of the two cell populations. Taken as a whole, we have made significant progress in defining the roles of these growth factors in stimulating tumor-driven osteolysis.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

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