title: Mesenchymal stem cells directly interact with breast cancer cells and promote tumor cell growth in vitro and in vivo.
abstract: Cellular interactions were investigated between human mesenchymal stem cells (MSC) and human breast cancer cells. Co-culture of the two cell populations was associated with an MSC-mediated growth stimulation of MDA-MB-231 breast cancer cells. A continuous expansion of tumor cell colonies was progressively surrounded by MSC(GFP) displaying elongated cell bodies. Moreover, some MSC(GFP) and MDA-MB-231(cherry) cells spontaneously generated hybrid/chimeric cell populations, demonstrating a dual (green fluorescent protein+cherry) fluorescence. During a co-culture of 5-6 days, MSC also induced expression of the GPI-anchored CD90 molecule in breast cancer cells, which could not be observed in a transwell assay, suggesting the requirement of direct cellular interactions. Indeed, MSC-mediated CD90 induction in the breast cancer cells could be partially blocked by a gap junction inhibitor and by inhibition of the notch signaling pathway, respectively. Similar findings were observed in vivo by which a subcutaneous injection of a co-culture of primary MSC with MDA-MB-231(GFP) cells into NOD/scid mice exhibited an about 10-fold increased tumor size and enhanced metastatic capacity as compared with the MDA-MB-231(GFP) mono-culture. Flow cytometric evaluation of the co-culture tumors revealed more than 90% of breast cancer cells with about 3% of CD90-positive cells, also suggesting an MSC-mediated in vivo induction of CD90 in MDA-MB-231 cells. Furthermore, immunohistochemical analysis demonstrated an elevated neovascularization and viability in the MSC/MDA-MB-231(GFP)-derived tumors. Together, these data suggested an MSC-mediated growth stimulation of breast cancer cells in vitro and in vivo by which the altered MSC morphology and the appearance of hybrid/chimeric cells and breast cancer-expressing CD90(+) cells indicate mutual cellular alterations.
authors.affiliation: 1 Biochemistry and Tumor Biology Lab, Gynecology Research Unit , Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany .
authors.forename: Katharina
authors.initials: K
authors.lastname: Mandel
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.forename: Anna
authors.initials: A
authors.lastname: Otte
authors.forename: Ralf
authors.initials: R
authors.lastname: Hass
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D047368:Tumor Burden