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

Science Advances
Charles E GastMelissa H Wong

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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Methods Mentioned

BETA
biopsies
fluorescence-activated cell sorting
FACS
two hybrid
Fluorescence
two independent hybrid
flow cytometry
biopsy
confocal microscopy
chips

Software Mentioned

ZEN
MATLAB
SoftWorx
rgl
MEMA
TrackMate
IncuCyte ZOOM
GeneSifter
R
Geospiza

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