Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival

Charles E. Gast, Alain D. Silk, Luai Zarour, Lara Riegler, Joshua G. Burkhart, Kyle T. Gustafson, Michael S. Parappilly, Minna Roh-Johnson, James R. Goodman, Brennan Olson, Mark Schmidt, John R. Swain, Paige S. Davies, Vidya Shasthri, Shinji Iizuka, Patrick Flynn, Spencer Watson, James Korkola, Sara A. Courtneidge, Jared M. FischerJerry Jaboin, Kevin G. Billingsley, Charles D. Lopez, Julja Burchard, Joe Gray, Lisa M. Coussens, Brett C. Sheppard, Melissa H. Wong

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish (US)
Article numbereaat7828
JournalScience Advances
Volume4
Issue number9
DOIs
StatePublished - Sep 12 2018

ASJC Scopus subject areas

  • General

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