@article{84feaa4f49e94cf780d67209e36985bb,
title = "Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival",
abstract = "High lethality rates associated with metastatic cancer highlight an urgent medical need for improved understanding of biologic mechanisms driving metastatic spread and identification of biomarkers predicting late-stage progression. Numerous neoplastic cell intrinsic and extrinsic mechanisms fuel tumor progression; however, mechanisms driving heterogeneity of neoplastic cells in solid tumors remain obscure. Increased mutational rates of neoplastic cells in stressed environments are implicated but cannot explain all aspects of tumor heterogeneity. We present evidence that fusion of neoplastic cells with leukocytes (for example, macrophages) contributes to tumor heterogeneity, resulting in cells exhibiting increased metastatic behavior. Fusion hybrids (cells harboring hematopoietic and epithelial properties) are readily detectible in cell culture and tumor-bearing mice. Further, hybrids enumerated in peripheral blood of human cancer patients correlate with disease stage and predict overall survival. This unique population of neoplastic cells provides a novel biomarker for tumor staging, as well as a potential therapeutic target for intervention.",
author = "Gast, {Charles E.} and Silk, {Alain D.} and Luai Zarour and Lara Riegler and Burkhart, {Joshua G.} and Gustafson, {Kyle T.} and Parappilly, {Michael S.} and Minna Roh-Johnson and Goodman, {James R.} and Brennan Olson and Mark Schmidt and Swain, {John R.} and Davies, {Paige S.} and Vidya Shasthri and Shinji Iizuka and Patrick Flynn and Spencer Watson and James Korkola and Courtneidge, {Sara A.} and Fischer, {Jared M.} and Jerry Jaboin and Billingsley, {Kevin G.} and Lopez, {Charles D.} and Julja Burchard and Joe Gray and Coussens, {Lisa M.} and Sheppard, {Brett C.} and Wong, {Melissa H.}",
note = "Funding Information: We acknowledge members of the OHSU Flow Cytometry Shared Resource and Advanced Light Microscopy Core at the Jungers Center for technical assistance, M. Troxell for pathology support, and A. Wong for technical assistance. Instrumentation used in this work was supported by grant number S10-RR023432 from the National Center for Research Resources, a component of the NIH, to the Advanced Light Microscopy Core at the OHSU Jungers Center. Research reported in this publication was supported by the NCI of the NIH under award numbers U54CA112970 and P30 CA069533 and by the National Heart Lung and Blood Institute of the NIH under award number T32HL007781. Additional support are as follows: NIH/T32GM071388, NCI/T32CA106195, and the American Skin Association (to C.E.G.); the Knight Cancer Institute Development Award/Veterans of Foreign Wars Ladies Auxiliary Group, the Phileo Foundation, and the Collins Medical Trust (to A.D.S.); and the Achievement to College Students Foundation Oregon (to K.T.G.). J.G.B. acknowledges support from NLM/5T15M007088-27. M.H.W. acknowledges support from the OHSU Center for Women{\textquoteright}s Health Circle of Giving Grant, the Newton Foundation, the Prospect Creek Foundation, the Brenden-Colson Center for Pancreatic Health, the Crohn{\textquoteright}s and Colitis Foundation, and NIH/NCI grants R01CA118235 and R21CA172334. L.M.C. acknowledges support from the NIH/NCI, Department of Defense Breast Cancer Research Program Era of Hope Scholar Expansion Award, Breast Cancer Research Foundation, the Susan G. Komen Foundation, and the Brenden-Colson Center for Pancreatic Health. Publisher Copyright: Copyright {\textcopyright} 2018 The Authors.",
year = "2018",
month = sep,
day = "12",
doi = "10.1126/sciadv.aat7828",
language = "English (US)",
volume = "4",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "9",
}