RT Journal Article
SR Electronic
T1 Omental Adipose Tissue–Derived Stromal Cells Promote Vascularization and Growth of Endometrial Tumors
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 771
OP 782
DO 10.1158/1078-0432.CCR-11-1916
VO 18
IS 3
A1 Klopp, Ann H.
A1 Zhang, Yan
A1 Solley, Travis
A1 Amaya-Manzanares, Felipe
A1 Marini, Frank
A1 Andreeff, Michael
A1 Debeb, Bisrat
A1 Woodward, Wendy
A1 Schmandt, Rosemarie
A1 Broaddus, Russell
A1 Lu, Karen
A1 Kolonin, Mikhail G.
YR 2012
UL http://clincancerres.aacrjournals.org/content/18/3/771.abstract
AB Purpose: 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. Experimental Design: 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. Clin Cancer Res; 18(3); 771–82. ©2011 AACR.This article is featured in Highlights of This Issue, p. 593