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肥胖与纤维化:为乳腺癌奠定基础。

Obesity and Fibrosis: Setting the Stage for Breast Cancer.

作者信息

Kuziel Genevra, Moore Brittney N, Arendt Lisa M

机构信息

Cancer Biology Graduate Program, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53705, USA.

Department of Comparative Biosciences, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.

出版信息

Cancers (Basel). 2023 May 26;15(11):2929. doi: 10.3390/cancers15112929.

Abstract

Obesity is a rising health concern and is linked to a worsened breast cancer prognosis. Tumor desmoplasia, which is characterized by elevated numbers of cancer-associated fibroblasts and the deposition of fibrillar collagens within the stroma, may contribute to the aggressive clinical behavior of breast cancer in obesity. A major component of the breast is adipose tissue, and fibrotic changes in adipose tissue due to obesity may contribute to breast cancer development and the biology of the resulting tumors. Adipose tissue fibrosis is a consequence of obesity that has multiple sources. Adipocytes and adipose-derived stromal cells secrete extracellular matrix composed of collagen family members and matricellular proteins that are altered by obesity. Adipose tissue also becomes a site of chronic, macrophage-driven inflammation. Macrophages exist as a diverse population within obese adipose tissue and mediate the development of fibrosis through the secretion of growth factors and matricellular proteins and interactions with other stromal cells. While weight loss is recommended to resolve obesity, the long-term effects of weight loss on adipose tissue fibrosis and inflammation within breast tissue are less clear. Increased fibrosis within breast tissue may increase the risk for tumor development as well as promote characteristics associated with tumor aggressiveness.

摘要

肥胖是一个日益严重的健康问题,并且与乳腺癌预后恶化有关。肿瘤促结缔组织增生,其特征是癌症相关成纤维细胞数量增加以及基质内纤维状胶原蛋白的沉积,可能导致肥胖患者乳腺癌的侵袭性临床行为。乳腺的一个主要成分是脂肪组织,肥胖导致的脂肪组织纤维化变化可能有助于乳腺癌的发展以及由此产生的肿瘤的生物学特性。脂肪组织纤维化是肥胖的一个后果,其来源多样。脂肪细胞和脂肪来源的基质细胞分泌由胶原蛋白家族成员和基质细胞蛋白组成的细胞外基质,这些成分会因肥胖而改变。脂肪组织也成为慢性、巨噬细胞驱动的炎症部位。巨噬细胞以多种群体形式存在于肥胖的脂肪组织中,并通过分泌生长因子和基质细胞蛋白以及与其他基质细胞相互作用来介导纤维化的发展。虽然建议通过减肥来解决肥胖问题,但减肥对乳腺组织中脂肪组织纤维化和炎症的长期影响尚不清楚。乳腺组织内纤维化增加可能会增加肿瘤发生的风险,并促进与肿瘤侵袭性相关的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/385d/10252103/85999b732fd1/cancers-15-02929-g001.jpg

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