Cancer cell's neuroendocrine feature can be acquired through cell-cell fusion during cancer-neural stem cell interaction

• Type of Material: Article
• Authors: Liyuan Yin, Sichuan University; Peizhen Hu, Cedars Sinai Medical Center Los Angeles; Xianping Shi, Cedars Sinai Medical Center Los Angele; Wei Qian, Emory University; Haiyen E. Zhau, Cedars Sinai Medical Center Los Angele; Stephen J. Pandol, Cedars Sinai Medical Center Los Angele; Michael S. Lewis, Greater Los Angeles Veterans Affairs Healthcare System; Leland W. K. Chung, Cedars Sinai Medical Center Los Angele; Ruoxiang Wang, Cedars Sinai Medical Center Los Angele
• Language: English
• Date: 2020-01-27
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-58118-z
• Title of Journal or Parent Work: Scientific Reports
• Volume: 10
• Issue: 1
• Start Page: 1216
• End Page: 1216
• Grant/Funding Information: This work was supported in part by NIH grants of CA098912 (LWKC) and CA112330 (RXW), and by DoD grants of CA170974 (LWKC) and PC040578 (RXW).
• Keywords: Neurons; Science & Technology - Other Topics; Vivo; Survival; Science & Technology; Multidisciplinary Sciences; Neurologic complications; Phenotype; Serum; Differentiation; LNCAP; Metastatic prostate cancer
• Research Categories: Health Sciences, Oncology; Biology, Cell; Biology, Neuroscience; Health Sciences, Immunology

Abstract

Advanced and therapy-resistant prostate tumors often display neural or neuroendocrine behavior. We assessed the consequences of prostate cancer cell interaction with neural cells, which are rich in the human prostate and resident of the prostate tumor. In 3-dimensional co-culture with neurospheres, red fluorescent human LNCaP cells formed agglomerates on the neurosphere surface. Upon induced neural differentiation, some red fluorescent cells showed morphology of fully differentiated neural cells, indicating fusion between the cancer and neural stem cells. These fusion hybrids survived for extended times in a quiescent state. A few eventually restarted cell division and propagated to form derivative hybrid progenies. Clones of the hybrid progenies were highly heterogeneous; most had lost prostatic and epithelial markers while some had acquired neural marker expression. These results indicate that cancer cells can fuse with bystander neural cells in the tumor microenvironment; and cancer cell fusion is a direct route to tumor cell heterogeneity.