Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival
| Autor: | Jerry J. Jaboin, Shinji Iizuka, Joshua Burkhart, Brennan Olson, Michael S. Parappilly, Charles D. Lopez, Minna Roh-Johnson, Lara Riegler, Kevin G. Billingsley, Vidya Shasthri, Paige S. Davies, Julja Burchard, Luai Zarour, Jared M. Fischer, Brett C. Sheppard, John R. Swain, James R. Goodman, S. Watson, Patrick A. Flynn, James E. Korkola, Joe W. Gray, Charles E. Gast, Mark Schmidt, Sara A. Courtneidge, Melissa H. Wong, Kyle T. Gustafson, Lisa M. Coussens, Alain D. Silk |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cell Survival Population Green Fluorescent Proteins Mice Transgenic Biology Hybrid Cells Cell Fusion 03 medical and health sciences Cell Line Tumor medicine Biomarkers Tumor Tumor Microenvironment Animals Humans education Research Articles Cancer education.field_of_study Tumor microenvironment Multidisciplinary Cell fusion Macrophages SciAdv r-articles Epithelial Cells medicine.disease Neoplastic Cells Circulating Xenograft Model Antitumor Assays 3. Good health Mice Inbred C57BL Pancreatic Neoplasms Haematopoiesis 030104 developmental biology Cell culture Tumor progression Karyotyping Cancer research Neoplastic cell Female Research Article Carcinoma Pancreatic Ductal |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Peripheral blood MФ–cancer cell fusion hybrids identified in cancer patients correlate with disease stage and overall survival. 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. |
| Databáze: | OpenAIRE |
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