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

被引:30
作者
Ribeiro, Ricardo [1 ,2 ,3 ]
Monteiro, Catia [3 ]
Silvestre, Ricardo [4 ,5 ]
Castela, Angela [6 ,7 ]
Coutinho, Helena [8 ]
Fraga, Avelino [2 ,9 ]
Principe, Paulo [9 ]
Lobato, Carlos [10 ]
Costa, Carla [6 ,11 ]
Cordeiro-da-Silva, Anabela [4 ,12 ]
Lopes, Jose Manuel [8 ,13 ]
Lopes, Carlos [2 ,14 ]
Medeiros, Rui [2 ,3 ]
机构
[1] Portuguese Inst Oncol, Mol Oncol Grp CI, Porto Ctr, P-4200072 Oporto, Portugal
[2] Univ Porto, Abel Salazar Biomed Sci Inst, ICBAS, P-4050313 Oporto, Portugal
[3] Portuguese League Canc NRNorte, Res Dept, LPCC, P-4200177 Oporto, Portugal
[4] Univ Porto, IBMC, Parasite Dis Grp, P-4150180 Oporto, Portugal
[5] CRL, CESPU, Adv Inst Hlth Sci N, Dept Sci, P-4585116 Gandra Prd, Portugal
[6] Univ Porto, Fac Med, Dept Biochem FCT U38, P-4200319 Oporto, Portugal
[7] Univ Porto IBMC UP, Inst Mol & Cell Biol, P-4150180 Oporto, Portugal
[8] Univ Porto, Fac Med, Dept Pathol & Oncol, P-4200319 Oporto, Portugal
[9] Porto Hosp Ctr, Dept Urol, P-4099001 Oporto, Portugal
[10] D Pedro V Mil Hosp, Dept Urol, P-4150113 Oporto, Portugal
[11] Univ Porto, Fac Med, Dept Expt Biol, P-4200319 Oporto, Portugal
[12] Univ Porto, Fac Pharm, Dept Biol Sci, P-4050313 Oporto, Portugal
[13] Univ Porto IPATIMUP, Inst Pathol & Mol Immunol, P-4200465 Oporto, Portugal
[14] Porto Hosp Ctr, Dept Pathol, P-4099001 Oporto, Portugal
关键词
adipose tissue; obesity; prostate cancer; progenitor cell; tumor microenvironment; PROMOTE CANCER PROGRESSION; STEM-CELLS; IN-VITRO; GROWTH; FAT; PROLIFERATION; FIBROBLASTS; METASTASIS; ADIPOCYTE; MIGRATION;
D O I
10.1258/ebm.2012.012131
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
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(-)CD0146(-) 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.
引用
收藏
页码:1155 / 1162
页数:8
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