title: Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis.
abstract: 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.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Yvonne S
authors.initials: YS
authors.lastname: Ziegler
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Nardulli
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006019:Glycolysis; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor