期刊
SCIENCE ADVANCES
卷 4, 期 9, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aat7828
关键词
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资金
- National Center for Research Resources of the NIH [S10-RR023432]
- NCI of the NIH [U54CA112970, P30 CA069533]
- National Heart Lung and Blood Institute of the NIH [T32HL007781]
- Knight Cancer Institute Development Award/Veterans of Foreign Wars Ladies Auxiliary Group
- Phileo Foundation
- Collins Medical Trust
- OHSU Center for Women's Health Circle of Giving Grant
- Newton Foundation
- Prospect Creek Foundation
- Brenden-Colson Center for Pancreatic Health
- Crohn's and Colitis Foundation
- NIH/NCI [R01CA118235, R21CA172334]
- Department of Defense Breast Cancer Research Program Era of Hope Scholar Expansion Award
- Breast Cancer Research Foundation
- Susan G. Komen Foundation
- American Skin Association
- Achievement to College Students Foundation Oregon
- [NIH/T32GM071388]
- [NCI/T32CA106195]
- [NLM/5T15M007088-27]
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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