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Dynamic interaction between breast cancer cells and osteoblastic tissue: Comparison of Two‐ and Three‐dimensional cultures

Breast cancer cell colonization of osteoblast monolayers grown in standard tissue culture (2D) is compared to colonization of a multi‐cell‐layer osteoblastic tissue (3D) grown in a specialized bioreactor. Colonization of 3D tissue recapitulates events observed in clinical samples including cancer penetration of tissue, growth of microcolonies, and formation of “Single cell file” commonly observed in end‐stage pathological bone tissue. By contrast, adherent cancer cell colonies did not penetrate 2D tissue and did not form cell files. Thus, it appears that 3D tissue is a more biologically (clinically) relevant model than 2D monolayers in which to study cancer cell interactions with osteoblastic tissue. This direct comparison of 2D and 3D formats is implemented using MC3T3‐E1 murine osteoblasts and MDA‐MB‐231 human metastatic breast cancer cells, or the metastasis‐suppressed line, MDA‐MB‐231BRMS1, for comparison. When osteoblasts were co‐cultured with metastatic cells, production of osteocalcin (a mineralization marker) decreased and secretion of the pro‐inflammatory cytokine IL‐6 increased in both 2D and 3D formats. Cancer cell penetration of the 3D tissue coincided with a changed osteoblast morphology from cuboidal to spindle‐shaped, and with osteoblasts alignment parallel to the cancer cells. Metastasis‐suppressed cells did not penetrate 3D tissue, did not cause a change in osteoblast morphology or align in rows. Moreover, they proliferated much less in the 3D culture than in the 2D culture in a manner similar to their growth in bone. In both systems, the cancer cells proliferated to a greater extent with immature osteoblasts compared to more mature osteoblasts. J. Cell. Physiol. 226: 2150–2158, 2011. © 2010 Wiley‐Liss, Inc.