title: Human ovarian carcinoma–associated  mesenchymal stem cells regulate  cancer stem cells and tumorigenesis  via altered BMP production.
abstract: Accumulating evidence suggests that mesenchymal stem cells (MSCs) are recruited to the tumor microenvironment; however, controversy exists regarding their role in solid tumors. In this study, we identified and confirmed the presence of carcinoma-associated MSCs (CA-MSCs) in the majority of human ovarian tumor samples that we analyzed. These CA-MSCs had a normal morphologic appearance, a normal karyotype, and were nontumorigenic. CA-MSCs were multipotent with capacity for differentiating into adipose, cartilage, and bone. When combined with tumor cells in vivo, CA-MSCs promoted tumor growth more effectively than did control MSCs. In vitro and in vivo studies suggested that CA-MSCs promoted tumor growth by increasing the number of cancer stem cells. Although CA-MSCs expressed traditional MSCs markers, they had an expression profile distinct from that of MSCs from healthy individuals, including increased expression of BMP2, BMP4, and BMP6. Importantly, BMP2 treatment in vitro mimicked the effects of CA-MSCs on cancer stem cells, while inhibiting BMP signaling in vitro and in vivo partly abrogated MSC-promoted tumor growth. Taken together, our data suggest that MSCs in the ovarian tumor microenvironment have an expression profile that promotes tumorigenesis and that BMP inhibition may be an effective therapeutic approach for ovarian cancer.
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
authors: Karen
authors: K
authors: McLean
authors: Yusong
authors: Y
authors: Gong
authors: Yunjung
authors: Y
authors: Choi
authors: Ning
authors: N
authors: Deng
authors: Kun
authors: K
authors: Yang
authors: Shoumei
authors: S
authors: Bai
authors: Lourdes
authors: L
authors: Cabrera
authors: Evan
authors: E
authors: Keller
authors: Laurie
authors: L
authors: McCauley
authors: Kathleen R
authors: KR
authors: Cho
authors: Ronald J
authors: RJ
authors: Buckanovich
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002469:Cell Separation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000166:cytology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D019485:Bone Morphogenetic Proteins