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Angiopoietin-like protein 2 facilitates non-small cell lung cancer progression by promoting the polarization of M2 tumor-associated macrophages
- Source :
- American journal of cancer research. 7(11)
- Publication Year :
- 2017
-
Abstract
- The functional phenotypes (M1 and M2) of tumor-associated macrophages (TAMs) are influenced by the tumor microenvironment (TME) and contribute greatly to the development of non-small cell lung cancer (NSCLC). However, the molecular mechanisms for TAM polarization remain unclear. Angiopoietin-like protein 2 (Angptl2) is involved in tumor progression. In this study, Angptl2 expression was aberrantly increased in NSCLC cells and positively correlated with TAM infiltration, tumor size and poor patient survival. Moreover, in vitro tumor cell-macrophage co-culture and recombinant protein stimulation revealed that Angptl2 fostered the M2 polarization of TAMs through the p65 nuclear factor-kappa B (NF-ĸB) pathway. In addition, Angptl2-promoted TAM enhanced proliferation, invasion, and migration of NSCLC cells and the tube formation of human umbilical vein endothelial cells (HUVECs). In vivo, TAM depletion inhibited the tumor growth induced by Angptl2. Here, for the first time, we determined that Angptl2 promoted the M2 polarization of TAMs and enhanced NSCLC progression. Interfering with Angptl2 might be an effective strategy for reprogramming TAM polarization in NSCLC, providing a promising therapy for NSCLC treatment.
Details
- ISSN :
- 21566976
- Volume :
- 7
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- American journal of cancer research
- Accession number :
- edsair.pmid..........5394e7256bbe784eab7c0baa1cb92bef