title: 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.
authors.affiliation: Molecular Oncology Group-CI, Portuguese Institute of Oncology, Rua Dr. António Bernardino Almeida, Porto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ribeiro
authors.forename: Cátia
authors.initials: C
authors.lastname: Monteiro
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.forename: Angela
authors.initials: A
authors.lastname: Castela
authors.forename: Helena
authors.initials: H
authors.lastname: Coutinho
authors.forename: Avelino
authors.initials: A
authors.lastname: Fraga
authors.forename: Paulo
authors.initials: P
authors.lastname: Príncipe
authors.forename: Carlos
authors.initials: C
authors.lastname: Lobato
authors.forename: Carla
authors.initials: C
authors.lastname: Costa
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D002454:Cell Differentiation; D011416:Complement Factor D / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C493488:CFD protein, human; D011416:Complement Factor D