Morad Vivian, Abrahamsson Annelie, Kjölhede Preben, Dabrosin Charlotta
Linköping University, Linköping, Sweden.
J Mammary Gland Biol Neoplasia. 2016 Jun;21(1-2):69-76. doi: 10.1007/s10911-016-9352-9. Epub 2016 Apr 8.
Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle. We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.
接触性类固醇会增加患乳腺癌的风险，但确切机制尚待阐明。微环境中的事件对致癌作用很重要。含有植物雌激素的饮食会影响乳腺微环境并改变患乳腺癌的风险。此前已有研究表明，雌激素可调节体内正常乳腺组织中瘦素、脂联素和血管内皮生长因子（VEGF）的细胞外水平。这些蛋白质在体内乳腺组织中是否相关，或者在西方饮食中植物雌激素的主要来源亚麻籽添加到饮食中是否会改变乳腺组织中的脂肪因子水平，目前尚不清楚。我们使用微透析技术对34名绝经前和绝经后女性的正常人体乳腺组织和腹部皮下脂肪中的蛋白质进行原位采样。在体外，使用乳腺癌细胞和原代人脂肪细胞进行共培养。在体内，在正常乳腺组织中，检测到VEGF与瘦素之间存在显著正相关。在脂肪组织中未发现相关性。与单独培养任何一种细胞类型相比，脂肪细胞和乳腺癌细胞的共培养本身增加了VEGF和瘦素的分泌，并增强了雌二醇的作用。在体外，抑制VEGF可减少瘦素的释放，而抑制瘦素对VEGF分泌没有影响。在一个月经周期内每天添加25克亚麻籽后，瘦素水平降低，脂联素水平升高。我们得出结论，VEGF和瘦素在体内正常人体乳腺组织中显著相关，并且饮食中添加亚麻籽会影响乳腺中的脂肪因子水平。
