Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer.
Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer.
复制标题
DOI：
10.3390/ijms17122060
复制
发表时间：
2016-12-08
影响因子：
5.6
通讯作者：
Waaga-Gasser AM
中科院分区：
文献类型：
--
作者：
Grimmig T;Moench R;Kreckel J;Haack S;Rueckert F;Rehder R;Tripathi S;Ribas C;Chandraker A;Germer CT;Gasser M;Waaga-Gasser AM
Toll样受体（TLR）信号转导在实体瘤的炎症微环境中发挥重要作用，并通过这种炎症介导的肿瘤生长。在此，我们研究了肿瘤细胞在其自身维持TLR表达过程中的作用，该过程不依赖于胰腺癌中炎症细胞和用于自动调节肿瘤生长信号传导的细胞因子环境。我们分析了TLR 2、TLR 4和TLR 9在原发性人类癌症中的表达，以及它们在几种已建立的胰腺癌中通过诱导活化对肿瘤生长的影响。对TLR刺激的胰腺癌细胞的VEGF/PDGF和抗凋亡Bcl-xL表达的活化信号传导途径以及肿瘤细胞生长进行了专门研究。原发性胰腺癌和细胞系表达TLR 2、TLR 4和TLR 9。TLR特异性刺激导致激活的MAP-激酶信号传导，最有可能是通过TLR诱导的VEGF和PDGF表达的自调节刺激。此外，TLR激活促进Bcl-xL的表达，并首次被证明可诱导胰腺癌中的肿瘤细胞增殖。这些发现强烈表明胰腺癌细胞使用特异性Toll样受体信号传导来促进肿瘤细胞增殖，并强调了TLR 2、TLR 4和TLR 9在胰腺癌中肿瘤细胞活化和增殖的这种自动调节过程中的特殊作用。
Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer.
登录
查看更多内容
影响因子：
4
作者：
Mai CW;Kang YB;Pichika MR
通讯作者：
Pichika MR
影响因子：
4.1
作者：
Liu, Jianhua;Yang, Jianguo;Gao, Meng
通讯作者：
Gao, Meng
影响因子：
8.4
作者：
Grimm, Martin;Kim, Mia;Gasser, Martin
通讯作者：
Gasser, Martin
影响因子：
5.2
作者：
Nandy D;Mukhopadhyay D
通讯作者：
Mukhopadhyay D
影响因子：
7.3
作者：
Muccioli M;Benencia F
通讯作者：
Benencia F