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Sci Adv. 2018 Sep 12;4(9):eaat7828. doi: 10.1126/sciadv.aat7828. eCollection 2018 Sep.

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

Author information

1
Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97239, USA.
2
Department of Surgery, Oregon Health & Science University, Portland, OR 97239, USA.
3
Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
4
Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USA.
5
Center for Early Detection Advanced Research, Oregon Health & Science University, Portland, OR 97239, USA.
6
Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA.
7
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
8
Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR 97239, USA.
9
Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
10
Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA.
11
Department of Radiation Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
12
Department of Computational Biology, Oregon Health & Science University, Portland, OR 97239, USA.

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.

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