A New In Vitro Model of Breast Cancer Metastasis to Bone
Abstract
The use of a bioreactor system has permitted the growth of osteoblasts lines and primary osteoblasts into osteoid, bone-like tissue. Over the course of months in culture, pre-osteoblasts matured to osteoblasts and eventually to osteocyte-like cells. This is the first system, that we are aware of, that permits this full range of osteogenesis. The system supports the growth of primary osteoblasts as well as osteoblast lines. The addition of breast cancer cells to the cultures, brought about profound effects on the osteoid tissue. The osteoblasts changed from cuboidal to spindle shaped and were less adherent to the substrate. The cancer cells aligned themselves with the osteoblasts into an Indian filing pattern. The breast cancer also penetrated the osteoid tissue. Extracellular matrix was degraded. These interactions of breast cancer cells with osteoblasts in vitro have not been previously detected. With both the primary osteoblasts and the MC3T3-E1 cell line, the cancer cells inhibited osteoblast gene expression of osteoblast differentiation proteins, but stimulated production of inflammatory cytokines. Microarray data of osteoblasts treated with growth medium versus conditioned medium from MDA-MB231 breast cancer cells supported the switch in pattern from differentiation to inflammation. In addition the microarray data indicated that several adhesion molecules were down regulated. Taken together, these data suggest that the osteoblasts in the bioreactor mimic those in metaphyseal areas of bone. The system should be useful as an in vivo surrogate.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2008
- Accession Number
- ADA486212
Entities
People
- Andrea M. Mastro
Organizations
- Pennsylvania State University