Laurent Victor, Nieto Laurence, Valet Philippe, Muller Catherine
Institut de pharmacologie et de biologie structurale, CNRS/université de Toulouse, UMR 5089, 205, route de Narbonne, BP 64182, 31077 Toulouse, France.
Inserm U1048, Institut des maladies métaboliques et cardiovasculaires de Toulouse (I2MC), 1, avenue Jean Poulhès, BP 84225, 31432 Toulouse Cedex 4, France.
Med Sci (Paris). 2014 Apr;30(4):398-404. doi: 10.1051/medsci/20143004013. Epub 2014 May 5.
Adipose tissue is found in close proximity whith many invasive cancers. In breast cancer, early local tumour invasion results in close interactions of cancer cells with fully differentiated adipocytes. Aside from their energy-storing function, mature adipocytes are also active endocrine cells prone to influence tumour behaviour through heterotypic signaling processes. After a short description of anatomical depots specificities of adipose tissue, we describe the phenotypic changes induced by tumor secretion in tumour-surrounding adipocytes. These cells (that we named CAA for cancer-associated adipocytes) by their ability to secrete pro-inflammatory cytokines, extra-cellular matrix proteins and proteases involved in its remodeling, as well as to release free fatty acid, stimulate tumor proliferation, invasiveness and drug resistance. These results support the concept that adipocytes participate in a deleterious crosstalk with cancer cells to support tumour progression, that might be amplified in obesity conditions and explain the poor prognosis of cancers observed in this subset of patients.
在许多浸润性癌症附近都能发现脂肪组织。在乳腺癌中,肿瘤早期局部浸润会导致癌细胞与完全分化的脂肪细胞密切相互作用。除了其能量储存功能外,成熟脂肪细胞也是活跃的内分泌细胞,易于通过异型信号传导过程影响肿瘤行为。在简要描述了脂肪组织的解剖学储存部位特异性后,我们描述了肿瘤分泌在肿瘤周围脂肪细胞中诱导的表型变化。这些细胞(我们将其命名为癌症相关脂肪细胞,即CAA)通过分泌促炎细胞因子、细胞外基质蛋白和参与其重塑的蛋白酶以及释放游离脂肪酸的能力,刺激肿瘤增殖、侵袭和耐药性。这些结果支持了这样一种概念,即脂肪细胞与癌细胞参与有害的串扰以支持肿瘤进展,这种串扰在肥胖情况下可能会加剧,并解释了在这一亚组患者中观察到的癌症预后不良的原因。