The Role of Parathyroid Hormone-Related Protein in Breast Cancer Mediated Osteolysis.
Annual rept. 30 Sep 94-29 Sep 95,
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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This proposal aims to study the role of PTHrP in breast cancer-mediated hypercalcemia and osteolysis. Results thus far demonstrate that I of 4 breast cancer cell lines screened MDA- MB-231 secretes PTHrP in vitro and this was not related to the presence of the estrogen receptor. In vivo data demonstrate that tumor-mediated osteolysis is associated with osteoclastic bone resorption at sites of tumor involvement and that PTHrP causes hypercalcemia when produced at sites distant from bone and locally by tumor in bone. Localized osteolysis mediated by PTHrP may occur without hypercalcemia. These data suggest that different tumor syndromes may be associated with PTHrP production and depend on the tumor location and degree of PTHrP expression. Additional In vivo data demonstrate that PTHrP overexpression in a breast cancer cell line is associated with an increased number of osteolytic metastases, hypercalcemia without an increase in plasma PTHrP concentration, and decreased survival. These data support the clinical findings that PTHrP, as a bone resorbing factor, may contribute to the ability of breast cancer to grow in bone and have important implications in the prognosis of women with newly diagnosed breast cancer treatment of breast cancer metastatic to bone.
- Anatomy and Physiology
- Medicine and Medical Research