C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma."

The canonical complement component 5a (C5a) receptor (C5aR) 1 has well-described roles in tumorigenesis but the contribution of the second receptor, C5aR2, is unclear. The present study demonstrates that B16.F0 melanoma cells express mRNA for both and and signal through ERK and p38 MAPKs in response to C5a. Despite this, C5a had no impact on melanoma cell proliferation or migration . studies demonstrated that the growth of B16.F0 melanoma tumors was increased in C5aR2 mice but reduced in C5aR1 mice and wild-type mice treated with a C5aR1 antagonist. Analysis of tumor-infiltrating leukocyte populations showed no significant differences between wild-type and C5aR2 mice. Conversely, percentages of myeloid-derived suppressor cells, macrophages, and regulatory T lymphocytes were lower in tumors from C5aR1 mice, whereas total (CD3) T lymphocytes and CD4 subsets were higher. Analysis of cytokine and chemokine levels also showed plasma IFN-γ was higher and tumor C-C motif chemokine ligand 2 was lower in the absence of C5aR1. The results suggest that C5aR1 signaling supports melanoma growth by promoting infiltration of immunosuppressive leukocyte populations into the tumor microenvironment, whereas C5aR2 has a more restricted but beneficial role in limiting tumor growth. Overall, these data support the potential of C5aR1-inhibitory therapies for melanoma.-Nabizadeh, J. A., Manthey, H. D., Panagides, N., Steyn, F. J., Lee, J. D., Li, X. X., Akhir, F. N. M., Chen, W., Boyle, G. M., Taylor, S. M., Woodruff, T. M., Rolfe, B. E. C5a receptors C5aR1 and C5aR2 mediate opposing pathologies in a mouse model of melanoma.


Journal Details

This article was published in the following journal.

Name: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Pages: fj201800980RR


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