title: Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors.
abstract: OBJECTIVE
  Adipose tissue contains a population of tumor-tropic mesenchymal progenitors, termed adipose stromal cells (ASC), which engraft in neighboring tumors to form supportive tumor stroma. We hypothesized that intra-abdominal visceral adipose tissue may contain a uniquely tumor-promoting population of ASC to account for the relationship between excess visceral adipose tissue and mortality of intra-abdominal cancers.
  
  
  METHODS
  To investigate this, we isolated and characterized ASC from intra-abdominal omental adipose tissue (O-ASC) and characterized their effects on endometrial cancer progression as compared with subcutaneous adipose-derived mesenchymal stromal cells (SC-ASC), bone marrow-derived mesenchymal stromal cells (BM-MSC), and lung fibroblasts. To model chronic recruitment of ASC by tumors, cells were injected metronomically into mice bearing Hec1a xenografts.
  
  
  RESULTS
  O-ASC expressed cell surface markers characteristic of BM-MSC and differentiated into mesenchymal lineages. Coculture with O-ASC increased endometrial cancer cell proliferation in vitro. Tumor tropism of O-ASC and SC-ASC for human Hec1a endometrial tumor xenografts was comparable, but O-ASC more potently promoted tumor growth. Compared with tumors in SC-ASC-injected mice, tumors in O-ASC-injected mice contained higher numbers of large tortuous desmin-positive blood vessels, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. O-ASC exhibited enhanced motility as compared with SC-ASC in response to Hec1a-secreted factors.
  
  
  CONCLUSIONS
  Visceral adipose tissue contains a population of multipotent MSCs that promote endometrial tumor growth more potently than MSCs from subcutaneous adipose tissue. We propose that O-ASCs recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Klopp
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Travis
authors.initials: T
authors.lastname: Solley
authors.forename: Felipe
authors.initials: F
authors.lastname: Amaya-Manzanares
authors.forename: Frank
authors.initials: F
authors.lastname: Marini
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Bisrat
authors.initials: B
authors.lastname: Debeb
authors.forename: Wendy
authors.initials: W
authors.lastname: Woodward
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Schmandt
authors.forename: Russell
authors.initials: R
authors.lastname: Broaddus
authors.forename: Karen
authors.initials: K
authors.lastname: Lu
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Kolonin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D009852:Omentum / Q000166:cytology*; D017154:Stromal Cells / Q000166:cytology*; D050151:Subcutaneous Fat / Q000166:cytology; D014183:Transplantation, Heterologous