RRC ID 66162
Author Hu L, Hayashi Y, Kidoya H, Takakura N.
Title Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization.
Journal Sci Rep
Abstract The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Consistent with this, treating WT mice with [Pyr1]Apelin-13 inhibited tumor growth. In MC38 tumors, only endothelial cells (ECs) strongly express APJ, a cognate receptor for Apelin, indicating that EC-derived Apelin might regulate tumor formation in an autocrine manner. Comparing with WT mice, larger numbers of vessels with narrower diameters were observed in tumors of Apelin knockout mice and lack of Apelin enhanced tumor hypoxia. Investigating immune cells in the tumor revealed that [Pyr1]Apelin-13 infusion induced the accumulation of CD8+ and CD4+ T cells in central areas. Moreover, RNA-sequencing analysis showed that Apelin induces chemokine CCL8 expression in ECs. Thus, enhancing anti-tumor immunity might be one of the mechanisms by which Apelin is involved in tumor growth. Our result indicated that increased CCL8 expression might induce CD8 +  T cells infiltration into tumor and tumor inhibition.
Volume 11(1)
Pages 14047
Published 2021-7-7
DOI 10.1038/s41598-021-93619-5
PII 10.1038/s41598-021-93619-5
PMID 34234274
PMC PMC8263715
MeSH Animals Apelin / genetics Apelin / metabolism* Apelin Receptors / genetics Apelin Receptors / metabolism Cell Line, Tumor Cell Proliferation Chemokine CCL8 / biosynthesis Chemotaxis, Leukocyte / genetics* Chemotaxis, Leukocyte / immunology Disease Models, Animal Endothelial Cells / metabolism* Humans Lymphocytes, Tumor-Infiltrating / immunology Lymphocytes, Tumor-Infiltrating / metabolism Lymphocytes, Tumor-Infiltrating / pathology Mice Mice, Knockout Neoplasms / etiology* Neoplasms / metabolism* Neoplasms / pathology Protein Binding Signal Transduction T-Lymphocyte Subsets / immunology T-Lymphocyte Subsets / metabolism T-Lymphocyte Subsets / pathology Tumor Microenvironment
IF 3.998
Human and Animal Cells LLC(RCB0558)