title: Dynamic interaction between breast cancer cells and osteoblastic tissue: comparison of two- and three-dimensional cultures.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, USA.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Krishnan
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Shuman
authors.forename: Donna M
authors.initials: DM
authors.lastname: Sosnoski
authors.forename: Ravi
authors.initials: R
authors.lastname: Dhurjati
authors.forename: Erwin A
authors.initials: EA
authors.lastname: Vogler
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Mastro
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D019149:Bioreactors; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002450:Cell Communication / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D010006:Osteoblasts / Q000473:pathology / Q000502:physiology*; D015675:Osteocalcin / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D015675:Osteocalcin