Accession Number : ADA300267

Title :   Mechanisms of Breast Cancer-Induced Osteolysis.

Descriptive Note : Annual rept. 15 JUL 94-14 JUL 95,

Corporate Author : JEWISH HOSPITAL ST LOUIS MO

Personal Author(s) : Teitelbaum, Steven L.

PDF Url : ADA300267

Report Date : 10 AUG 1995

Pagination or Media Count : 21

Abstract : Breast cancer often metastasizes to bone causing fractures and hypercalcemia due to osteolysis. This process likely involves recruitment by the cancer cells of osteoclasts from precursors. A coculture system was used to demonstrate that human T47D breast cancer cells promote differentiation of osteoclasts from precursors. This process was dependent on the concentration of cancer cells and the presence of 1,25(OH)2D3. Clonal sublines of T47D) were derived which lacked the ability to promote osteoclast differentiation. Using in vitro cancer cell attachment assays to human bone marrow stromal cells, two populations, adherent and non-adherent, of MDA-MB-231 cells, were isolated. when each population was tested in vivo for bone metastasis, the adherent cells showed a higher frequency of osteolytic lesions. It was established that MDA-MB-231 cells attach to human bone marrow stromal cells in part by alpha(v) Integrins. Cells were selected which expressed either high or undetectable levels of the alpha(4)Beta(3)integrin. When these cells were tested for bone metastasis in vivo, it was determined the cells that did not express alpha/beta(3) expressing cells, or bone stroma adherent cells showed that both expressed low levels of the integrin. From these results we conclude that alpha/beta(3) is not required for breast cancer metastasis to bone. Finally, our data demonstrate that cancer cells derived from a bone tumor metastasize to bone more frequently than the parental cells.

Descriptors :   *NEOPLASMS, *CANCER, *MAMMARY GLANDS, *BONES, *BREAST CANCER, FREQUENCY, CELLS, IN VIVO ANALYSIS, LESIONS, METASTASIS.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE