Department of Biology, Lafayette College, Easton, PA 18042, USA.
Cell Immunol. 2013 Apr;282(2):136-45. doi: 10.1016/j.cellimm.2013.04.014. Epub 2013 May 14.
Previously we reported that Myd88 contributed to tumor progression. To begin to decipher what may be inducing Myd88 dependent signaling we focused on proteins that could function as damage associated molecular pattern molecules (DAMPs) since DAMPs have been reported to be secreted by tumors, and certain DAMPs mediate effects through toll-like receptors. A screen of mammary carcinoma for DAMP expression showed HMGB1 and HSP60 were significantly elevated relative to normal mammary epithelium, and targeting these DAMPs, or receptors for these DAMPs influenced growth of tumor cells. Moreover, analysis using a Myd88 inhibitory peptide suggested that HMGB1 mediated its effects in a Myd88 dependent manner, and inhibiting Myd88 function decreased HMGB1 and HSP60 gene expression. Collectively, these data suggest that HMGB1 and HSP60 contribute to growth of mammary carcinoma cells, HMGB1 accomplishes this, at least in part, through Myd88 dependent signaling, and these DAMPs are expressed in a Myd88 dependent manner.
此前我们曾报道过，Myd88 有助于肿瘤的进展。为了开始破译可能诱导 Myd88 依赖性信号的物质，我们专注于可能作为损伤相关分子模式分子 (DAMPs) 发挥作用的蛋白质，因为据报道 DAMPs 可由肿瘤分泌，并且某些 DAMPs 通过 Toll 样受体介导作用。对乳腺癌中 DAMPs 表达的筛选显示，HMGB1 和 HSP60 与正常乳腺上皮相比显著升高，针对这些 DAMPs 或 DAMPs 的受体可影响肿瘤细胞的生长。此外，使用 Myd88 抑制肽的分析表明，HMGB1 以 Myd88 依赖性方式介导其作用，并且抑制 Myd88 功能可降低 HMGB1 和 HSP60 基因表达。总的来说，这些数据表明 HMGB1 和 HSP60 有助于乳腺癌细胞的生长，HMGB1 至少部分通过 Myd88 依赖性信号传导来实现这一点，并且这些 DAMPs 以 Myd88 依赖性方式表达。
