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Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells.
J Surg Res. 2001 Sep; 100(1):18-24.JS

Abstract

BACKGROUND

Breast cancer metastasis to bone causes resorption of the mineralized matrix by osteoclasts. Macrophage colony stimulating factor (M-CSF)and receptor activator of the NF-kappaB ligand (RANKL) are produced by stromal cells and are essential for osteoclast formation. The human breast cancer cell line, MDA-MB-231, reliably forms bone metastases in a murine model and stimulates osteoclast formation in culture. We hypothesized that MDA-MB-231 stimulates osteoclast formation through secretion of M-CSF and/or RANKL.

MATERIALS AND METHODS

We cocultured MDA-MB-231 and a bone marrow derived cell line, UAMS-33, and evaluated the expression of M-CSF and RANKL mRNA. Osteoclast formation was assessed using these cells added to hematopoietic cell cultures.

RESULTS

MDA-MB-231 exhibited constitutive expression of M-CSF mRNA. As expected, addition of recombinant M-CSF (30 ng/ml) and RANKL (30 ng/ml) to hematopoietic osteoclast precursors supported osteoclast formation, while the addition of soluble RANKL alone or MDA-231 without added RANKL did not. Notably, coculture of MDA-231 with hematopoietic cells and added soluble RANKL stimulated significant osteoclast formation, indicating that MDA-231 served as an effective source for M-CSF. MDA-231 did not express RANKL. However, when cocultured with the murine bone marrow stromal cell line UAMS-33, RANKL expression was significantly increased in the latter cells. MDA-231 also stimulated osteoclast formation in coculture with UAMS-33 and hematopoietic cells.

CONCLUSIONS

We conclude that MDA-MB-231 increases osteoclast formation by secreting adequate amounts of M-CSF protein and enhancing the expression of RANKL by stromal support cells. The ability to stimulate osteoclasts may explain the ability to metastasize to bone.

Authors+Show Affiliations

Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11516200

Citation

Mancino, A T., et al. "Breast Cancer Increases Osteoclastogenesis By Secreting M-CSF and Upregulating RANKL in Stromal Cells." The Journal of Surgical Research, vol. 100, no. 1, 2001, pp. 18-24.
Mancino AT, Klimberg VS, Yamamoto M, et al. Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells. J Surg Res. 2001;100(1):18-24.
Mancino, A. T., Klimberg, V. S., Yamamoto, M., Manolagas, S. C., & Abe, E. (2001). Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells. The Journal of Surgical Research, 100(1), 18-24.
Mancino AT, et al. Breast Cancer Increases Osteoclastogenesis By Secreting M-CSF and Upregulating RANKL in Stromal Cells. J Surg Res. 2001;100(1):18-24. PubMed PMID: 11516200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Breast cancer increases osteoclastogenesis by secreting M-CSF and upregulating RANKL in stromal cells. AU - Mancino,A T, AU - Klimberg,V S, AU - Yamamoto,M, AU - Manolagas,S C, AU - Abe,E, PY - 2001/8/23/pubmed PY - 2001/9/21/medline PY - 2001/8/23/entrez SP - 18 EP - 24 JF - The Journal of surgical research JO - J Surg Res VL - 100 IS - 1 N2 - BACKGROUND: Breast cancer metastasis to bone causes resorption of the mineralized matrix by osteoclasts. Macrophage colony stimulating factor (M-CSF)and receptor activator of the NF-kappaB ligand (RANKL) are produced by stromal cells and are essential for osteoclast formation. The human breast cancer cell line, MDA-MB-231, reliably forms bone metastases in a murine model and stimulates osteoclast formation in culture. We hypothesized that MDA-MB-231 stimulates osteoclast formation through secretion of M-CSF and/or RANKL. MATERIALS AND METHODS: We cocultured MDA-MB-231 and a bone marrow derived cell line, UAMS-33, and evaluated the expression of M-CSF and RANKL mRNA. Osteoclast formation was assessed using these cells added to hematopoietic cell cultures. RESULTS: MDA-MB-231 exhibited constitutive expression of M-CSF mRNA. As expected, addition of recombinant M-CSF (30 ng/ml) and RANKL (30 ng/ml) to hematopoietic osteoclast precursors supported osteoclast formation, while the addition of soluble RANKL alone or MDA-231 without added RANKL did not. Notably, coculture of MDA-231 with hematopoietic cells and added soluble RANKL stimulated significant osteoclast formation, indicating that MDA-231 served as an effective source for M-CSF. MDA-231 did not express RANKL. However, when cocultured with the murine bone marrow stromal cell line UAMS-33, RANKL expression was significantly increased in the latter cells. MDA-231 also stimulated osteoclast formation in coculture with UAMS-33 and hematopoietic cells. CONCLUSIONS: We conclude that MDA-MB-231 increases osteoclast formation by secreting adequate amounts of M-CSF protein and enhancing the expression of RANKL by stromal support cells. The ability to stimulate osteoclasts may explain the ability to metastasize to bone. SN - 0022-4804 UR - https://www.unboundmedicine.com/medline/citation/11516200/Breast_cancer_increases_osteoclastogenesis_by_secreting_M_CSF_and_upregulating_RANKL_in_stromal_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(01)96204-3 DB - PRIME DP - Unbound Medicine ER -