Title | Programmed cell removal by calreticulin in tissue homeostasis and cancer. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Feng M, Marjon KD, Zhu F, Weissman-Tsukamoto R, Levett A, Sullivan K, Kao KS, Markovic M, Bump PA, Jackson HM, Choi TS, Chen J, Banuelos AM, Liu J, Gip P, Cheng L, Wang D, Weissman IL |
Journal | Nat Commun |
Volume | 9 |
Issue | 1 |
Pagination | 3194 |
Date Published | 2018 08 10 |
ISSN | 2041-1723 |
Keywords | Adult, Aged, Aged, 80 and over, Animals, Binding Sites, Calreticulin, Cell Line, Tumor, Cell Membrane, Cell Survival, Cellular Senescence, Female, Hematopoiesis, Homeostasis, Humans, Ligands, Macrophages, Male, Mice, Middle Aged, Neoplasms, Neutrophils, Phagocytosis, Polysaccharides |
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. |
DOI | 10.1038/s41467-018-05211-7 |
Alternate Journal | Nat Commun |
PubMed ID | 30097573 |
PubMed Central ID | PMC6086865 |
Grant List | K99CA201075/R00CA201075 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) / International T32DK098132 / / U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) / International R01CA086017 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) / International R00 CA201075 / CA / NCI NIH HHS / United States R56AI118464 / / U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) / International P01CA139490 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) / International R56 AI118464 / AI / NIAID NIH HHS / United States DFS-22-16 / / Damon Runyon Cancer Research Foundation (Damon Runyon) / International |
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