Mechanisms of Breast Cancer-Induced Osteolysis.
Abstract
We had previously shown that the MDA-MB-231 breast cancer cells selected for rapid adherence to primary bone marrow stroma metastasize to bone more rapidly than cancer cells which do not adhere to the stromal matrix. Comparison of surface integrins between stroma adherent and nonradherent cells indicated that the adherent cells expressed lower levels of the integrin alpha(v)Beta(3). Based on this observation we isolated cancer cells which expressed either high or undetectable levels of the integrin. When these cells were tested for bone metastasis in vivo, it was determined that the high a(v)Beta(3) expressing cancer cells metastasized to bone up to ten times less frequently that the cancer cells which do not express the integrin. Thus expression of a(v)Beta(3) inversely correlates with frequency of bone metastasis. In addition to alpha(v)Beta(3), we have determined no significant change in the expression levels of alpha1-6, Beta1 and Beta5 integrins between the parental MDA-MB-231 cells and bone tumors derived from them. In addition, by serial passage of metastatic tumors in vivo, we have isolated populations of MDA-MB-231 cells which are highly metastatic to bone, liver or kidney. These organ selective metastatic cells provide a new tool for identifying molecules responsible for bone metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1996
- Accession Number
- ADA323303
Entities
People
- Steven L. Teitelbaum