BMC Med:肥胖男性的前列腺周围脂肪或促进前列腺癌发展
2012-09-27 生物谷 生物谷
前列腺癌是男性最常见的癌症之一,早期治疗通常是非常成功的。然而像其他类型癌症一样,肥胖会增加侵略性前列腺疾病的风险。新的研究发表在BMC Medicine杂志上,研究证实超重或肥胖的男性前列腺癌患者前列腺周围的脂肪为促进癌细胞的生长提供了一个有利的环境。 脂肪是一个普遍被低估的物质,它不仅储存能量,也会分泌一系列广泛生长因子如细胞因子和激素包括瘦素、脂联素等,瘦素、脂联素在保护身体免受感染和疾病
前列腺癌是男性最常见的癌症之一,早期治疗通常是非常成功的。然而像其他类型癌症一样,肥胖会增加侵略性前列腺疾病的风险。新的研究发表在BMC Medicine杂志上,研究证实超重或肥胖的男性前列腺癌患者前列腺周围的脂肪为促进癌细胞的生长提供了一个有利的环境。
脂肪是一个普遍被低估的物质,它不仅储存能量,也会分泌一系列广泛生长因子如细胞因子和激素包括瘦素、脂联素等,瘦素、脂联素在保护身体免受感染和疾病的免疫系统发挥关键作用。但是过多的脂肪会导致这些免疫系统失控,增加糖尿病、心血管疾病和癌症的风险。
Gema Frühbeck教授和Ricardo Ribeiro博士领导的一个国际研究小组从接受手术治疗后前列腺疾病患者中得到前列腺周围的脂肪。样品包括男性良性前列腺增生症者(BPH)、前列腺癌者(PC)以及其他癌症类型患者的脂肪。这些参试人员分为瘦(BMI <25)型或超重/肥胖(BMI> 25)型。
无论什么类型的前列腺疾病,相比瘦的男人,体重超重的男性前列腺周围的脂肪中有不同程度的基因表达。这些基因包括编码在免疫和炎症、细胞生长和增殖、脂肪代谢和细胞程序性死亡过程中发挥作用的蛋白质,如LEP编码蛋白质瘦素,ANGPT1编码血管生成素1。此外,更多的基因表达在前列腺增生和前列腺癌、癌症和非癌症者的前列腺中发生了改变。
医生Ribeiro表示:对于一个日益肥胖人群,了解脂肪尤其是前列腺周围的脂肪是如何影响前列腺癌细胞的生长可能为实现个性化治疗带来帮助。
doi:10.1186/1741-7015-10-108
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PMID:
Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue
Ricardo Ribeiro, Catia Monteiro, Victoria Catalan, Pingzhao Hu, Virginia Cunha, Amaia Rodriguez, Javier Gomez-Ambrosi, Avelino Fraga, Paulo Principe, Carlos Lobato, Francisco Lobo, Antonio Morais, Vitor Silva, Jose Sanches-Magalhaes, Jorge Oliveira, Francisco Pina, Carlos Lopes, Rui Medeiros and Gema Fruhbeck
Background Periprostatic (PP) adipose tissue surrounds the prostate, an organ with high predisposition to become malignant. Frequently growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer.
Methods Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to donors' body mass index characteristics (OB/OW vs. lean) and prostate disease (extra prostatic cancer vs. organ confined prostate cancer vs. benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks.
Results In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (e.g. FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related with the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients.
Conclusions Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.
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