Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
J Immunol. 2011 Feb 1;186(3):1781-9. doi: 10.4049/jimmunol.1002998. Epub 2010 Dec 22.
Cancer-related inflammation profoundly affects tumor progression. Tumor-associated macrophages (TAMs) are known regulators of that inflammation, but the factors that initiate cancer-related inflammation are poorly understood. Tumor invasiveness and poor clinical outcome are linked to increased expression of cell surface-associated vacuolar adenosine triphosphatases. The a2 isoform vacuolar adenosine triphosphatase is found on the surface on many solid tumors, and we have identified a peptide cleaved from a2 isoform vacuolar adenosine triphosphatase called a2NTD. a2NTD has properties necessary to induce monocytes into a pro-oncogenic TAM phenotype. The peptide upregulated both pro- and anti-inflammatory mediators. These included IL-1β and IL-10, which are important in promoting inflammation and immune escape by tumor cells. The secretion of inflammatory cytokine IL-1β was dependent on ATP, K(+) efflux, and reactive oxygen species, all mediators that activate the inflammasome. These findings describe a mechanism by which tumor cells affect the maturation of TAMs via a nontraditional cytokine-like signal, the a2NTD peptide.
癌症相关炎症会深刻影响肿瘤的进展。肿瘤相关巨噬细胞（TAMs）是已知的炎症调节者，但启动癌症相关炎症的因素知之甚少。肿瘤侵袭性和不良临床结局与细胞表面相关液泡三磷酸腺苷酶的表达增加有关。液泡三磷酸腺苷酶的 a2 同工型存在于许多实体瘤的表面，我们已经鉴定出一种从 a2 同工型液泡三磷酸腺苷酶切割而来的肽，称为 a2NTD。a2NTD 具有诱导单核细胞向促癌性 TAM 表型转化的必要特性。该肽上调了促炎和抗炎介质。其中包括在促进肿瘤细胞炎症和免疫逃逸方面起重要作用的 IL-1β 和 IL-10。炎性细胞因子 IL-1β 的分泌依赖于 ATP、K+外排和活性氧，这些都是激活炎症小体的介质。这些发现描述了肿瘤细胞通过一种非传统的细胞因子样信号，即 a2NTD 肽，影响 TAMs 成熟的机制。
