Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: a functional and MR imaging pilot study.
Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: a functional and MR imaging pilot study.
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肥胖前列腺癌患者的前列腺周围脂肪组织促进肿瘤和内皮细胞增殖：一项功能性和磁共振成像试点研究。
DOI：
10.1002/pros.22756
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发表时间：
2014
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影响因子：
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通讯作者：
Doll,JenniferA
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作者：
Venkatasubramanian,PalamadaiN;Brendler,CharlesB;Plunkett,BethA;Crawford,SusanE;Fitchev,PhilipS;Morgan,Gina;Cornwell,MonaL;McGuire,MichaelS;Wyrwicz,AliceM;Doll,JenniferA
背景肥胖，特别是内脏肥胖，使前列腺癌（PCa）患者的预后较差，并且前列腺周围脂肪（PPA）组织厚度或密度的增加与更具侵袭性的疾病呈正相关。然而，这种活性的细胞机制仍不清楚。因此，在这项初步研究中，我们评估了 PPA 组织分泌物的功能活性，并与瘦、超重和肥胖 PCa 患者的皮下脂肪 (SQA) 组织进行比较，建立了 PPA 的生化特征。 方法从接受手术前列腺切除的 PCa 患者中收集脂肪组织。通过组织学和磁共振（MR）技术对组织进行分析。外植体组织培养分泌物用于 PCa 和内皮细胞的增殖测定。结果与从瘦超重者和 SQA 组织获得的 PPA 相比，从肥胖患者获得的 PPA 分泌物在 PCa 和内皮细胞中显着更具增殖性。与此一致的是，与 SQA 组织相比，PPA 微血管密度增加，T2 弛豫时间缩短，并且我们观察到 T2 与肿瘤分期之间存在适度的负相关。此外，使用磁共振波谱法获得的不饱和脂肪酸与饱和脂肪酸的比率显示出与格里森评分呈适度的负相关。结论这些初步数据表明，PPA 刺激 PCa 细胞增殖和血管生成，而肥胖则强化了这种活性，从而产生了一个机制假设来解释肥胖 PCa 患者中观察到的较差预后。我们的试点研究还表明，MR 技术可能有助于进一步阐明肥胖与 PCa 进展之间的关系。Prostate 74:326–335, 2014。© 2013 Wiley periodicals, Inc.
BACKGROUNDObesity, particularly visceral adiposity, confers a worse prognosis for prostate cancer (PCa) patients, and increasing periprostatic adipose (PPA) tissue thickness or density is positively associated with more aggressive disease. However, the cellular mechanism of this activity remains unclear. Therefore, in this pilot study, we assessed the functional activity of PPA tissue secretions and established a biochemical profile of PPA as compared to subcutaneous adipose (SQA) tissues from lean, overweight and obese PCa patients.METHODSAdipose tissues were collected from PCa patients undergoing surgical prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR) techniques. Explant tissue culture secretions were used in proliferation assays on PCa and endothelial cells.RESULTSPPA secretions obtained from obese patients were significantly more pro‐proliferative in both PCa and endothelial cells as compared to PPA obtained from leanor overweightmen and SQA tissues. Consistent with this, PPA microvessel density was increased, and the T2relaxation time was decreased, compared to SQA tissues, and we observed a modest, inverse correlation between the T2and tumor stage. Moreover, the ratio of unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a modest, inverse correlation with Gleason score.CONCLUSIONSThese pilot data show that PPA stimulates PCa cell proliferation and angiogenesis and that obesity intensifies this activity, thus generating a mechanistic hypothesis to explain the worse prognosis observed in obese PCa patients. Our pilot study also shows that MR technology may be useful in further elucidating the relationship between obesity and PCa progression.Prostate 74:326–335, 2014. © 2013 Wiley Periodicals, Inc.