title: Stromal Cells Derived from Visceral and Obese Adipose Tissue Promote Growth of Ovarian Cancers.
abstract: Obesity, and in particular visceral obesity, has been associated with an increased risk of developing cancers as well as higher rates of mortality following diagnosis. The impact of obesity on adipose-derived stromal cells (ASC), which contribute to the formation of tumor stroma, is unknown. Here we hypothesized that visceral source and diet-induced obesity (DIO) changes the ASC phenotype, contributing to the tumor promoting effects of obesity. We found that ASC isolated from subcutaneous (SC-ASC) and visceral (V-ASC) white adipose tissue(WAT) of lean(Le) and obese(Ob) mice exhibited similar mesenchymal cell surface markers expression, and had comparable effects on ovarian cancer cell proliferation and migration. Obese and visceral derived ASC proliferated slower and exhibited impaired differentiation into adipocytes and osteocytes in vitro as compared to ASC derived from subcutaneous WAT of lean mice. Intraperitoneal co-injection of ovarian cancer cells with obese or visceral derived ASC, but not lean SC-ASC, increased growth of intraperitoneal ID8 tumors as compared to controls. Obese and V-ASC increased stromal infiltration of inflammatory cells, including CD3+ T cells and F4/80+ macrophages. Obese and visceral derived ASC, but not lean SC-ASC, increased expression of chemotactic factors IL-6, MIP-2, and MCP-1 when cultured with tumor cells. Overall, these results demonstrate that obese and V-ASC have a unique phenotype, with more limited proliferation and differentiation capacity but enhanced expression of chemotactic factors in response to malignant cells which support infiltration of inflammatory cells and support tumor growth and dissemination.
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Aleksandra
authors: A
authors: Nowicka
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Travis N
authors: TN
authors: Solley
authors: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Caimiao
authors: C
authors: Wei
authors: Department of Physics and Astronomy, Rice University, Houston, Texas, United States of America.
authors: Aaroh
authors: A
authors: Parikh
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Laurence
authors: L
authors: Court
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Jared K
authors: JK
authors: Burks
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Michael
authors: M
authors: Andreeff
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Wendy A
authors: WA
authors: Woodward
authors: The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors: Ali
authors: A
authors: Dadbin
authors: The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors: Mikhail G
authors: MG
authors: Kolonin
authors: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Karen H
authors: KH
authors: Lu
authors: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: Ann H
authors: AH
authors: Klopp
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000096:biosynthesis; D018920:Coculture Techniques; D005260:Female; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D018925:Chemokines