Ziegler Yvonne S, Moresco James J, Yates John R, Nardulli Ann M
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
PLoS One. 2016 Jun 29;11(6):e0158296. doi: 10.1371/journal.pone.0158296. eCollection 2016.
Cancer cells secrete factors that influence adjacent cell behavior and can lead to enhanced proliferation and metastasis. To better understand the role of these factors in oncogenesis and disease progression, estrogen and progesterone receptor positive MCF-7 cells, triple negative breast cancer MDA-MB-231, DT22, and DT28 cells, and MCF-10A non-transformed mammary epithelial cells were grown in 3D cultures. A special emphasis was placed on triple negative breast cancer since these tumors are highly aggressive and no targeted treatments are currently available. The breast cancer cells secreted factors of variable potency that stimulated proliferation of the relatively quiescent MCF-10A cells. The conditioned medium from each cell line was subjected to mass spectrometry analysis and a variety of secreted proteins were identified including glycolytic enzymes, proteases, protease inhibitors, extracellular matrix proteins, and insulin-like growth factor binding proteins. An investigation of the secretome from each cell line yielded clues about strategies used for breast cancer proliferation and metastasis. Some of the proteins we identified may be useful in the development of a serum-based test for breast cancer detection, diagnosis, prognosis, and monitoring.
癌细胞分泌影响相邻细胞行为的因子，可导致增殖和转移增强。为了更好地理解这些因子在肿瘤发生和疾病进展中的作用，雌激素和孕激素受体阳性的MCF-7细胞、三阴性乳腺癌MDA-MB-231、DT22和DT28细胞以及MCF-10A非转化乳腺上皮细胞在三维培养中生长。特别关注三阴性乳腺癌，因为这些肿瘤具有高度侵袭性，目前尚无靶向治疗方法。乳腺癌细胞分泌不同效力的因子，刺激相对静止的MCF-10A细胞增殖。对每个细胞系的条件培养基进行质谱分析，鉴定出多种分泌蛋白，包括糖酵解酶、蛋白酶、蛋白酶抑制剂、细胞外基质蛋白和胰岛素样生长因子结合蛋白。对每个细胞系分泌组的研究揭示了乳腺癌增殖和转移所采用的策略线索。我们鉴定出一些蛋白质可能有助于开发基于血清的乳腺癌检测、诊断、预后和监测测试。
