Programmed cell removal by calreticulin in tissue homeostasis and cancer

Mingye Feng (), Kristopher D. Marjon, Fangfang Zhu, Rachel Weissman-Tsukamoto, Aaron Levett, Katie Sullivan, Kevin S. Kao, Maxim Markovic, Paul A. Bump, Hannah M. Jackson, Timothy S. Choi, Jing Chen, Allison M. Banuelos, Jie Liu, Phung Gip, Lei Cheng, Denong Wang and Irving L. Weissman ()
Additional contact information
Mingye Feng: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Kristopher D. Marjon: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Fangfang Zhu: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Rachel Weissman-Tsukamoto: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Aaron Levett: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Katie Sullivan: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Kevin S. Kao: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Maxim Markovic: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Paul A. Bump: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Hannah M. Jackson: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Timothy S. Choi: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Jing Chen: City of Hope Comprehensive Cancer Center
Allison M. Banuelos: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Jie Liu: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Phung Gip: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University
Lei Cheng: State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and West China Hospital of Stomatology, Sichuan University
Denong Wang: SRI International
Irving L. Weissman: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to “labeling” by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.

Date: 2018
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DOI: 10.1038/s41467-018-05211-7

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