Neem leaf glycoprotein regulates function of tumor associated M2 macrophages in hypoxic tumor core: Critical role of IL-10/STAT3 signaling.
Mol Immunol
; 80: 1-10, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27776244
ABSTRACT
Heterogeneous tumor microenvironment (TME), broadly divided into tumor core and peripheral sub-microenvironments, differentially polarize normal macrophages into a different form known as tumor associated M2 macrophages (M2TAMs) to promote tumor growth. In view of the extensive immune-editing role of NLGP, here, we have observed that NLGP is effective to convert M2TAMs (CD11b+F4/80high) to M1 (CD11b+F4/80low) more prominently in tumor core, along with downregulation of other M2 associated markers, like, ManR, Ym1, Fizz1. High IL-10IL-12 ratio at tumor core was downregulated in NLGP treated melanoma bearing mice. Decrease in IL-10 by NLGP is again associated with the decrease in hypoxia, as indicated by prominent downregulation of HIF1α and VEGF, particularly at tumor core. Macrophages exposed to hypoxic tumor core lysates in vitro exhibited high IL-10, HIF1α and VEGF expression that was significantly downregulated by NLGP. Further evidences suggest M2TAM to M1 conversion by NLGP is associated with STAT3-regulated IL-10 dependent pathway without affecting the IL-4 dependent one. Such TAM modulatory functions of NLGP might help in the restriction of melanoma growth by increasing the proportion of M1 TAMs in tumor core that helps in prevention of tumor relapse and dissemination of the tumor mass.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Plantas
/
Melanoma Experimental
/
Transdução de Sinais
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Macrófagos
/
Antineoplásicos Fitogênicos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Índia