MicroRNA-155 deficiency enhances the recruitment and functions of myeloid-derived suppressor cells in tumor microenvironment and promotes solid tumor growth.

Abstract

Immune cells in tumor microenvironment play a prominent role in tumor progression and metastasis. MicroRNA-155 (miR-155) represents an important player in innate and adaptive immunity by regulating differentiation, maturation and activation of macrophages, dendritic cells, B cells and T cells. However, the role of miR-155 expression in immune cells in solid tumor development is less elucidated. Our current study showed that both B16-F10 melanoma and Lewis lung carcinoma tumors grew much faster in bic/miR-155 knockout (miR-155(-/-) ) mice along with an increase of myeloid-derived suppressor cells (MDSCs) accumulation in tumors, compared to that in wild-type mice. Bone marrow transplantation study showed that bone marrow miR-155 deficiency could replicate the above tumor-promoting phenotype. In vitro study demonstrated that tumor-infiltrating miR-155(-/-) MDSCs showed greater migration ability and expressed higher level of multiple chemokines. Furthermore, we found that the level of HIF-1α, a direct target of miR-155, was increased in miR-155 deficient MDSCs, and that the increased HIF-1α upregulated CXCL1, CXCL3 and CXCL8 expression in MDSCs, contributing to the enhanced recruitment of miR-155(-/-) MDSCs to the tumors. Moreover, miR-155(-/-) MDSCs showed enhanced immunosuppressive and pro-angiogenic capacities. Taken together, our study, for the first time, demonstrated that miR-155 deficiency promoted solid tumor growth through increasing the recruitment of MDSCs to tumor microenvironment and enhancing the tumor-promoting functions of the recruited MDSCs. Thus, upregulating miR-155 expression in MDSCs may be developed as a therapeutic approach to halt tumor development.

• Authors: Junfeng Wang, Fang Yu, Xuemei Jia, Stephen Iwanowycz, Yuzhen Wang, Shiang Huang, Walden Ai, Daping Fan
• Journal: International journal of cancer (Int J Cancer) Vol. 136 Issue 6 Pg. E602-13 (Mar 15 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25143000 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• MicroRNAs
• Mirn155 microRNA, mouse

Topics

• Animals
• Carcinoma, Lewis Lung (pathology)
• Cell Movement
• Cell Proliferation
• Female
• Hypoxia-Inducible Factor 1, alpha Subunit (physiology)
• Melanoma, Experimental (pathology)
• Mice
• Mice, Inbred C57BL
• MicroRNAs (physiology)
• Myeloid Cells (physiology)
• Neoplasms (pathology)
• Tumor Microenvironment