Department of Biomedicine; University of Bergen; Bergen, Norway.
Adipocyte. 2013 Jul 1;2(3):176-83. doi: 10.4161/adip.24472. Epub 2013 Apr 19.
Most tumors are typified by a chronic, unresolved inflammatory response that potentiates angiogenesis and therefore enables tumor progression. We have determined that dysfunctional tumor-associated adipocytes contribute to tumor-associated inflammation. In three tumor models, tumor-associated adipose tissue was characterized by thin and fragile adipocyte membranes, necrosis, robust expression of the pro-inflammatory factor HMGB1, and loss of the lipid storage mediator, perilipin-1. By transmission electron microscopy, macrophages in tumor-associated adipose tissue contained lipid droplets and resembled foam cells, which are commonly observed in inflamed tissues. In vitro co-culture studies showed that tumor-associated adipose tissue conditioned-medium stimulated monocyte-to-macrophage differentiation, adhesion, spreading, and lipid uptake. Compared with normal adipose tissue, tumor-associated adipose tissue secreted 3-fold higher levels of IL-6 and IL-6 was sufficient to stimulate macrophage differentiation and adhesion. These results suggest that, in tumors, loss of adipocyte specification, necrosis, and scavenging of adipocyte debris directly activates macrophages and contributes to tumor-associated inflammation. Thus, adipocyte dysfunction may facilitate tumor progression, especially in tumors closely aligned with adipose tissue, in particular, breast cancer.
大多数肿瘤的特点是慢性、未解决的炎症反应，这种反应增强了血管生成，从而促进了肿瘤的进展。我们已经确定，功能失调的肿瘤相关脂肪细胞有助于肿瘤相关炎症。在三种肿瘤模型中，肿瘤相关脂肪组织的特征是脂肪细胞膜薄而脆弱、坏死、促炎因子 HMGB1 表达强烈以及脂质储存介质 perilipin-1 丢失。通过透射电子显微镜观察，肿瘤相关脂肪组织中的巨噬细胞含有脂质滴，类似于在炎症组织中常见的泡沫细胞。体外共培养研究表明，肿瘤相关脂肪组织条件培养基刺激单核细胞向巨噬细胞分化、黏附、展开和脂质摄取。与正常脂肪组织相比，肿瘤相关脂肪组织分泌的 IL-6 水平高出 3 倍，而 IL-6 足以刺激巨噬细胞分化和黏附。这些结果表明，在肿瘤中，脂肪细胞特异性丧失、坏死和脂肪细胞碎片的清除直接激活了巨噬细胞，并有助于肿瘤相关炎症。因此，脂肪细胞功能障碍可能促进肿瘤的进展，尤其是在与脂肪组织密切相关的肿瘤中，特别是乳腺癌。
