Wolf Marietta, Brochhausen Christoph, Ramakrishnan Vignesh, Iberl Sabine, Roth Jonas, Seitz Stephan, Burkhardt Ralph, Stadler Sonja C
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany.
Department of Operative Dentistry and Periodontology, Center for Dental Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg im Breisgau, Germany.
Cancers (Basel). 2024 Oct 17;16(20):3515. doi: 10.3390/cancers16203515.
Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients. TNBC tissue sections from normal-weight (BMI) and overweight/obese patients (BMI) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin. At the invasive tumor front, positive cells were counted in tumor adjacent adipose tissue (AT) and within cancer tissue (CT). Further, the size of the tumor-adjacent and distant mammary adipocytes was determined in perilipin stained sections. Expression of ANGPTL4, CD36 and FABP4, proteins involved in fatty acid metabolism, was analyzed in marginal tumor cells using an immune reactive score. Overweight/obese TNBC patients had significantly larger adipocytes, higher numbers of CD163+ macrophages (BMI: 2.80 vs. BMI: 10.45; = 0.011) and lower numbers of CD31+ (BMI: 4.20 vs. BMI: 2.40; = 0.018) and CD34+ (BMI: 14.60 vs. BMI: 5.20; = 0.045) cells as markers of angiogenesis in the AT as well as a higher frequency of cancer-associated-fibroblast-like cells in the AT and CT (BMI: 7.60 vs. BMI: 25.39 in total; = 0.001). Moreover, expression of CD36 (BMI: 2.15 vs. BMI: 2.60; = 0.041) and ANGPTL4 (BMI: 6.00 vs. BMI: 9.80; = 0.026) was elevated in the TNBC cells of overweight/obese patients. Our data suggest BMI-related changes in the TME of overweight/obese TNBC patients, including hypertrophied adipocytes, reduced vascularization, more M2-like macrophages and CAF-like cells, and an increase in the expression of fatty acid metabolizing proteins in marginal tumor cells, all contributing to a more tumor-promoting, immunosuppressive environment.
肥胖是包括乳腺癌在内的多种癌症的风险因素。在本研究中，我们旨在从组织学角度对超重/肥胖与正常体重的三阴性乳腺癌（TNBC）患者肿瘤微环境（TME）中的脂肪组织进行特征描述。对正常体重（BMI）和超重/肥胖患者（BMI）的TNBC组织切片用抗CD68、CD163、CD31、CD34和波形蛋白的抗体进行染色。在侵袭性肿瘤前沿，对肿瘤邻近脂肪组织（AT）和癌组织（CT）中的阳性细胞进行计数。此外，在脂滴包被蛋白染色切片中测定肿瘤邻近和远处乳腺脂肪细胞的大小。使用免疫反应评分分析边缘肿瘤细胞中参与脂肪酸代谢的蛋白ANGPTL4、CD36和FABP4的表达。超重/肥胖的TNBC患者具有明显更大的脂肪细胞、更多的CD163+巨噬细胞（BMI：2.80对BMI：10.45；P = 0.011）以及更少的CD31+（BMI：4.20对BMI：2.40；P = 0.018）和CD34+（BMI：14.60对BMI：5.20；P = 0.045）细胞作为AT中血管生成的标志物，并且AT和CT中癌症相关成纤维细胞样细胞的频率更高（总体BMI：7.60对BMI：25.39；P = 0.001）。此外，超重/肥胖患者的TNBC细胞中CD36（BMI：2.15对BMI：2.60；P = 0.041）和ANGPTL4（BMI：6.00对BMI：9.80；P = 0.026）的表达升高。我们的数据表明超重/肥胖的TNBC患者的TME存在与BMI相关的变化，包括肥大的脂肪细胞、血管化减少、更多的M2样巨噬细胞和CAF样细胞，以及边缘肿瘤细胞中脂肪酸代谢蛋白表达增加，所有这些都促成了一个更有利于肿瘤生长、免疫抑制的环境。
