The plasticity of macrophages with selective functional phenotypes partially arises in respective to their microenvironment. Tumor-associated macrophages (TAMs) may promote
disease progression with
tumor specific manner. Here we report that in pediatric malignant soft-tissue
tumors, the presence of TAMs and expression of
adiponectin (APN) are heterogeneous. Both APN and TAMs had high expression in
rhabdomyosarcoma, especially in the malignant subtype,
alveolar rhabdomyosarcoma. To investigate the mode of action of APN on TAM activation, a murine MN/MCA1
sarcoma model was used. The Results revealed that exogenous APN had no effect on MN/MCA1 proliferation but
tumor size was markedly reduced in apn(-/-) mice versus WT controls. The accumulation of TAMs in apn(-/-) mice was also reduced which correlated to downregulated serum levels of MCP-1. Likewise, TAMs in apn(-/-) mice exhibited a M1-like phenotype, characterized by increase in MHC II(high) population and M1 phenotypic markers, such as iNOS gene and serum TNF-α accompanied by a decrease in M2 markers, namely YM1 gene and serum
IL-10. In addition, APN deficiency increased the number of CD4(+) T cells, CD8(+) T cells and NK cells in
tumors and reduced
tumor metastasis. The altered phenotype of TAMs in apn(-/-) mice was associated with a marked decrease in phospho-p38 and treatment with a
p38 MAPK inhibitor significantly reduced
tumor size and increased MHC II expression on TAMs in WT mice, implying
p38 MAPK signaling pathway may contribute to APN-mediated TAM polarization. Collectively, our findings suggest that APN may have a potential role in regulating
soft tissue sarcoma growth.