Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas. Department of Surgery, University of Texas Health Science Center, Tyler, Texas.
Department of Cellular & Molecular Biology, University of Texas Health Science Center, Tyler, Texas.
Clin Cancer Res. 2016 Sep 1;22(17):4517-24. doi: 10.1158/1078-0432.CCR-16-0135. Epub 2016 Apr 8.
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.
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, TGFβ2 concentration in exosome samples was measured, breast cells incubated with the exosomes and effect (epithelial-mesenchymal transition, EMT) on EMT-related proteins [E-cadherin, α-smooth muscle actin (α-SMA), filamentous (F)-actin and vimentin] measured.
Human milk exosomes entered benign and malignant breast cells. The greatest change in wean milk protein was in TGFβ2 (P = 0.01). Exosomes with a high (but not low) level of TGFβ2 led to EMT in both cancer and benign cells, based on (i) change in cell morphology, actin cytoskeleton, and loss of cell-cell junction structure and (ii) increased α-SMA and vimentin and decreased E-cadherin.
TGFβ2 is significantly upregulated in breast milk exosomes during weaning/early involution. Breast milk exosomes containing high levels of TGFβ2 induce changes in both benign and malignant breast epithelial cells, consistent with the development and progression of breast cancer, suggesting a role for high TGFβ2-expressing breast milk exosomes in influencing breast cancer risk. Clin Cancer Res; 22(17); 4517-24. ©2016 AACR.
妊娠会使所有女性在分娩后至少 5 年内增加乳腺癌风险。在哺乳和退化过程中，乳房微环境变得具有促进肿瘤生长的作用。外泌体在哺乳等生理过程中提供细胞间通讯，但也存在于乳腺癌中。我们确定了来自健康哺乳期女性的乳汁外泌体中的分子是否调节乳腺癌的发生和发展。
13 名哺乳期女性提供了 3 种（过渡、成熟和断奶）奶样。提取外泌体并标记 MCF7 和 MCF10A 乳腺细胞。测量了与乳腺癌相关的 6 种蛋白质的表达。基于这些发现，测量了外泌体样本中的 TGFβ2 浓度，用外泌体孵育乳腺细胞，并测量 EMT 相关蛋白（上皮-间充质转化，EMT）[E-钙黏蛋白、α-平滑肌肌动蛋白（α-SMA）、丝状（F）-肌动蛋白和波形蛋白]的变化。
人乳外泌体进入良性和恶性乳腺细胞。断奶奶蛋白中 TGFβ2 变化最大（P=0.01）。基于（i）细胞形态、肌动蛋白细胞骨架和细胞间连接结构的丧失，以及（ii）α-SMA 和波形蛋白增加和 E-钙黏蛋白减少，具有高（但不是低）TGFβ2 水平的外泌体导致癌症和良性细胞的 EMT。
在断奶/早期退化过程中，TGFβ2 在乳腺外泌体中显著上调。含有高浓度 TGFβ2 的乳腺外泌体诱导良性和恶性乳腺上皮细胞发生变化，与乳腺癌的发生和发展一致，提示高 TGFβ2 表达的乳腺外泌体在影响乳腺癌风险方面发挥作用。临床癌症研究；22（17）；4517-24. 2016 年 AACR。
