Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis

• Published in: PloS one Vol. 11; no. 6; p. e0158296
• Main Authors: Ziegler, Yvonne S, Moresco, James J, Yates, 3rd, John R, Nardulli, Ann M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.06.2016; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Biomarkers, Tumor - blood; Breast - pathology; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - diagnosis; Cancer; Cancer metastasis; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Conditioning; Development and progression; Diagnosis; Disease detection; Early Detection of Cancer - methods; Epithelial cells; Estrogens; Extracellular matrix; Female; Glycolysis; Humans; Insulin; Mammary gland; Mass spectrometry; Mass spectroscopy; Medical diagnosis; Medical prognosis; Medicine and Health Sciences; Metastases; Neoplasm Metastasis; Physiological aspects; Progesterone; Progesterone receptors; Prognosis; Protease inhibitors; Proteinase inhibitors; Proteins; Risk factors; Secretome; Tumorigenesis; Tumors; Massachusetts; La Jolla California; California; United States > US; Illinois
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158296

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.