An New in Vitro Model of Breast Cancer Metastasis to Bone
Annual rept. 15 Mar 2006-14 Mar 2007
PENNSYLVANIA STATE UNIV UNIVERSITY PARK
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Human hFOB 1.19 and murine MC3T3-E1 osteoblasts grew for extended periods up to 10 months in a specialized bioreactor. Over time the cells formed multilayers and a collagenous matrix with mineralized nodules and small chips of bone . The number of cell layers in the bone-like tissue peaked at about 30 to 60 days and then declined. This change was reflected in the cell morphology. Wth time, the osteoblasts transitioned from multilayer cuboidal cells to flat osteocyte-like cells. We characterized the response of MC3T3-E1 bone-like tissue at various stages of maturity to metastatic human MDA-MB-231 breast cancer cells using a variety of approaches. The cancer cells attached, grew, and penetrated the matrix. Within 2 days of coculture, the cancer cells replicated and organized into linear files. Close inspection of both 2D optical sections and 3D reconstructions revealed concomitant remodeling of the tissue. Over 3 days of co-culture, cuboidal osteoblasts became elongated and aligned themselves with cancer cells. The osteoblasts responded with production of IL-6, a characteristic osteoblast inflammatory stress cytokine. These data support our idea that the bioreactor will serve as a useful in vitro model to study the interaction of metastatic breast cancer cells and osteoblasts.
- Anatomy and Physiology
- Medicine and Medical Research