Exosomes in Human Breast Milk Promote EMT
Exosomes in Human Breast Milk Promote EMT
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DOI：
10.1158/1078-0432.ccr-16-0135
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发表时间：
2016-09-01
影响因子：
11.5
通讯作者：
Sauter, Edward R.
中科院分区：
文献类型：
--
作者：
Qin, Wenyi;Tsukasaki, Yoshikazu;Sauter, Edward R.
目的：怀孕增加了所有妇女在分娩后至少5年内患乳腺癌的风险。在断奶和退化期间，乳房微环境变得促进肿瘤。外泌体在哺乳等生理过程中提供细胞间通讯，但也在乳腺癌中提供。我们确定是否从健康的哺乳期妇女的牛奶外泌体的分子调节乳腺癌的发展和progression of breast cancer.Experimental Design：13名哺乳期妇女提供了三个（过渡，成熟，和断奶）的牛奶样品。提取外泌体并标记MCF 7和MCF 10A乳腺细胞。测量了与乳腺癌相关的六种蛋白质的表达。在此基础上，检测外泌体中TGF β 2的浓度，检测外泌体对乳腺细胞的作用，并检测EMT对EMT相关蛋白[E-cadherin、α-平滑肌肌动蛋白（α-SMA）、丝状肌动蛋白（F）-actin和波形蛋白（vimentin）]的影响。最大的变化是在断奶乳蛋白转化生长因子β 2（P = 0.01）。高（但不低）TGF β 2水平的外泌体导致癌细胞和良性细胞中的EMT，基于（i）细胞形态、肌动蛋白细胞骨架和细胞连接结构的损失的变化，以及（ii）增加的α-SMA和波形蛋白和减少的E-cadherin.Conclusions：在断奶/早期退化期间，TGF β 2在母乳外泌体中显著上调。含有高水平TGF β 2的母乳外泌体诱导良性和恶性乳腺上皮细胞的变化，与乳腺癌的发展和进展一致，表明高TGF β 2表达的母乳外泌体在影响乳腺癌风险中的作用。(C)2016年AACR。
Purpose: Pregnancy increases breast cancer risk for all women for at least 5 years after parturition. During weaning and involution, the breast microenvironment becomes tumor promotional. Exosomes provide cell-cell communication during physiologic processes such as lactation, but also in breast cancer. We determined whether molecules in milk exosomes from healthy lactating women modulate the development and progression of breast cancer.Experimental Design: Thirteen nursing women provided three (transitional, mature, and wean) milk samples. Exosomes were extracted and MCF7 and MCF10A breast cells labeled. The expression of six proteins linked to breast cancer was measured. On the basis of the findings, TGF beta 2 concentration in exosome samples was measured, breast cells incubated with the exosomes and effect (epithelial-mesenchymal transition, EMT) on EMT-related proteins [E-cadherin, a-smooth muscle actin (alpha-SMA), filamentous (F)-actin and vimentin] measured.Results: Human milk exosomes entered benign and malignant breast cells. The greatest change in wean milk protein was in TGF beta 2 (P = 0.01). Exosomes with a high (but not low) level of TGF beta 2 led to EMT in both cancer and benign cells, based on (i) change in cell morphology, actin cytoskeleton, and loss of cellcell junction structure and (ii) increased alpha-SMA and vimentin and decreased E-cadherin.Conclusions: TGF beta 2 is significantly upregulated in breast milk exosomes during weaning/early involution. Breast milk exosomes containing high levels of TGF beta 2 induce changes in both benign and malignant breast epithelial cells, consistent with the development and progression of breast cancer, suggesting a role for high TGF beta 2-expressing breast milk exosomes in influencing breast cancer risk. (C) 2016 AACR.