Scientific Publications by FDA Staff

Cancer Res 2005 Aug 15;65(16):7370-7

Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis.

Koblinski JE, Kaplan-Singer BR, VanOsdol SJ, Wu M, Engbring JA, Wang S, Goldsmith CM, Piper JT, Vostal JG, Harms JF, Welch DR, Kleinman HK

Kleinman HK, Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Room 433,Bldg 30,30 Convent Dr, Bethesda, MD 20892 USA Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA Natl Inst Dent & Craniofacial Res, Genet Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA Capital Univ Med Sci, Fac Stomatol, Beijing, Peoples R China US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Hershey, PA USA Univ Alabama, Dept Pathol, Ctr Comprehens Canc, Birmingham, AL 35294 USA

Skeletal metastases occur with high incidence in patients with breast cancer and cause long-term skeletal morbidity. Osteonectin (SPARC, BM-40) is a bone matrix factor that is an in vitro chemoattractant for breast and prostate cancer cells. Increased expression of osteonectin is found in malignant breast tumors. We infected MDA-231 breast cancer cells with an adenovirus expressing osteonectin to examine the role of osteonectin expression in breast cancer cells and its effect on metastasis, in particular to bone. Expression of osteonectin did not affect MDA-231 cell proliferation, apoptosis, migration, cell aggregation, or protease cleavage of collagen IV. However, in vitro invasion of these osteonectin-infected cells through Matrigel and colony formation on Matrigel was decreased. Interestingly, high osteonectin expression in MDA-231 cells inhibited metastasis in a dose-dependent manner to many different organs including bone. The reduction in metastasis may be due to decreased platelet-tumor cell aggregation, because exogenous osteonectin inhibited platelet aggregation in vitro and the high osteonectin expression in MDA-231 cells reduced tumor cell-induced thrombocytopenia in vivo compared with control-infected cells. These studies suggest that high endogenous expression of osteonectin in breast cancer cells may reduce metastasis via reduced invasive activity and reduced tumor cell-platelet aggregation.