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

Venkatesh Krishnan, Laurie A. Shuman, Donna M. Sosnoski, Ravi Dhurjati, Erwin A. Vogler, Andrea Marie Mastro

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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.

Original languageEnglish (US)
Pages (from-to)2150-2158
Number of pages9
JournalJournal of Cellular Physiology
Volume226
Issue number8
DOIs
StatePublished - Aug 1 2011

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Osteoblasts
Cell culture
Cells
Tissue
Breast Neoplasms
Neoplasms
Monolayers
Bone
Tissue culture
Neoplasm Metastasis
Osteocalcin
Bioreactors
Bone Development
Interleukin-6
Cell Communication
Cytokines
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Krishnan, Venkatesh ; Shuman, Laurie A. ; Sosnoski, Donna M. ; Dhurjati, Ravi ; Vogler, Erwin A. ; Mastro, Andrea Marie. / Dynamic interaction between breast cancer cells and osteoblastic tissue : Comparison of Two- and Three-dimensional cultures. In: Journal of Cellular Physiology. 2011 ; Vol. 226, No. 8. pp. 2150-2158.
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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.",
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Dynamic interaction between breast cancer cells and osteoblastic tissue : Comparison of Two- and Three-dimensional cultures. / Krishnan, Venkatesh; Shuman, Laurie A.; Sosnoski, Donna M.; Dhurjati, Ravi; Vogler, Erwin A.; Mastro, Andrea Marie.

In: Journal of Cellular Physiology, Vol. 226, No. 8, 01.08.2011, p. 2150-2158.

Research output: Contribution to journalArticle

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AU - Krishnan, Venkatesh

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AU - Vogler, Erwin A.

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