A New In Vitro Model of Breast Cancer Metastasis to Bone
Abstract
Osteoblasts (OB) grew into bone-like tissue in a 3D model system. Pre-OB matured to OB and eventually to osteocyte-like cells. These cells met the criteria of osteocytes based on shape and protein expression. In addition, the density was similar to that reported for calvaria bone. The 3-D system was used to examine the interaction of metastatic breast cancer cells, MDA-MB-231, with OB. The cancer cells brought about profound effects on the osteoid tissue. The OB changed from cuboidal to spindle shape.The cancer cells aligned into an "Indian filing" pattern, and penetrated the osteoid. Metastasis suppressed MDA-MB-231-BRMS cells attached loosely to the osteoblasts but did not colonize or penetrate the tissue. Using RT-PCR, we found that metastatic cancer cells downregulated OB differentiation proteins but increased inflammatory cytokines. We have tried to modify these effects by changing the oxidative status of the microenvironment with selenium and by adding drugs commonly used to treat metastatic breast cancer, zoledronc acid (ZOL). ZOL's main known target is the osteoclast but we found that it clearly affects osteoblasts and cancer cells. The OB morphology changes were inhibited. Selenium supplementation caused changes in the osteoblast cell morphology and permitted cancer cell growth but in a different pattern than seen in the deficient cultures. In summary the model mimics in vivo bone metastatic colonization. The results show that the osteblasts are a major target.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2010
- Accession Number
- ADA533775
Entities
People
- Andrea M. Mastro
- Carol V. Gay
- Erwin A. Vogler
Organizations
- Pennsylvania State University