Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination

Chih Wei Chou, Chia Nung Hung, Cheryl Hsiang Ling Chiu, Xi Tan, Meizhen Chen, Chien Chin Chen, Moawiz Saeed, Che Wei Hsu, Michael A. Liss, Chiou Miin Wang, Zhao Lai, Nathaniel Alvarez, Pawel A. Osmulski, Maria E. Gaczynska, Li Ling Lin, Veronica Ortega, Nameer B. Kirma, Kexin Xu, Zhijie Liu, Addanki P. KumarJosephine A. Taverna, Gopalrao V.N. Velagaleti, Chun Liang Chen, Zhao Zhang, Tim Hui Ming Huang

Producción científica: Articlerevisión exhaustiva

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Resumen

While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.

Idioma originalEnglish (US)
Número de artículo6569
PublicaciónNature communications
Volumen14
N.º1
DOI
EstadoPublished - dic 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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