Cancer Therapy: Preclinical Omental Adipose Tissue–Derived Stromal Cells Promote Vascularization and Growth of Endometrial Tumors

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 comparedwith subcutaneous adipose-derivedmesenchymal stromal cells (SC-ASC), bonemarrow–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 tropismofO-ASC and SC-ASC for humanHec1a endometrial tumor xenografts was comparable, butO-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 growthmore potently thanMSCs fromsubcutaneous adipose tissue.Wepropose thatO-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.