Human periprostatic white adipose tissue is rich in stromal progenitor cells and a potential source of prostate tumor stroma

Abstract

A body of growing evidence now implicates white adipose tissue as a relevant source of stromal progenitor cells recruited to the tumor microenvironment to form supportive tumor stroma. While the role of periprostatic (PP) adipose tissue in prostate cancer progression has been barely appreciated, we sought to determine the progenitor cell population in PP adipose tissue and the association with prostate cancer. We isolated and characterized CD31(-)CD34(+)CD45(-)CD146(-) progenitor cells (adipose-derived stem cells [ASC]) in paired samples of PP and preperitoneal visceral adipose tissue from prostate tissue and peripheral blood mononuclear cells of prostate cancer and nodular prostatic hyperplasia patients. ASC were quantified by flow cytometry and confirmed through target gene expression. Here we show a significantly higher amount of ASC in PP than in visceral adipose tissue, independent of body mass index and prostatic disease. In the prostate, ASC are increased in cancer compared with prostatic nodular hyperplasia patients. Concordantly, adipsin gene (CFD) expression, which is known to be up-regulated in adipose stem cells, was overexpressed in PP adipose tissue, in the prostate of cancer patients and in prostate CD31(-)CD34(+)CD45(-)CD146(-) sorted cells. ASC were found at higher levels in the blood of prostate cancer patients simultaneously overweight/obese. Present findings indicate that PP adipose tissue is a reservoir of progenitor cells with the potential to migrate towards prostate tumors, although its clinical significance merits further evaluation.

Association of obesity and circulating adipose stromal cells among breast cancer survivors

“…Increased number of circulating ASCs was first linked to cancer-free obese individuals by Bellows et al (70). Similar observations were reported for obese colorectal and prostate cancer patients (69, 71). In this regard, our finding of circulating ASCs among obese breast cancer survivors further validates the previous reports and extends the association between circulating ASCs and obesity to a women's cancer type that has been long associated with obesity.…”

“…Accrual of obese women with no history of breast cancer would shed light on this important question. Lastly, despite the common immunophenotype shared by circulating ASCs and their adipose tissue-derived counterparts, it was difficult to pinpoint the true origin of circulating ASCs as detected in the current and previously published studies (69-71). Comparison of the gene expression signature between these two sources of human ASCs, preferably from the same individual, may reveal additional commonality and potential distinctions between these two cell populations.…”

“…This obesity-associated circulating cell population expressed high levels of the hematopoietic cell-specific marker (CD34 + ), but low levels of the endothelial- (CD31 − ) and macrophage/monocyte-specific (CD45 − ) markers. Intriguingly, the abundance of circulating ASCs was found to be even higher in obese colorectal and prostate cancer patients than their cancer-free obese controls (69, 71). Thus, circulating ASCs may not only serve as a novel biomarker for obesity-related pathological progression but also play an active role in cancer progression and metastasis.…”

Contribution of Adipose Tissue to Development of Cancer

“…Although ASCs are primarily localized to fat depots, circulating ASCs have also been detected in obese individuals and cancer patients, with greater levels observed in obese patients bearing colon, prostate, or breast cancers (relative to lean) (142, 327, 367, 462). Additionally, relative to ASCs from lean adipose, ASCs isolated from obese adipose show enhanced potential to traffic to breast tumors in both humans and mice (366, 464).…”

“…Ribiero et al observed higher levels of circulating ASCs in the blood of overweight or obese compared to lean prostate cancer patients (327). The authors also reported that periprostatic adipose tissue of prostate cancer patients bore significantly higher numbers of ASCs than nearby visceral adipose tissue, independent of BMI.…”