肿瘤微环境中的异质性基质信号控制着胰腺癌的转移。
Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer.
作者信息
Rucki Agnieszka A, Foley Kelly, Zhang Pingbo, Xiao Qian, Kleponis Jennifer, Wu Annie A, Sharma Rajni, Mo Guanglan, Liu Angen, Van Eyk Jennifer, Jaffee Elizabeth M, Zheng Lei
机构信息
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
出版信息
Cancer Res. 2017 Jan 1;77(1):41-52. doi: 10.1158/0008-5472.CAN-16-1383. Epub 2016 Nov 7.
Understanding how stromal signals regulate the development of pancreatic ductal adenocarcinoma (PDAC) may suggest novel therapeutic interventions in this disease. In this study, we assessed the metastatic role of stromal signals suggested to be important in the PDAC microenvironment. Src and IGF-1R phosphorylated the prometastatic molecule Annexin A2 (AnxA2) at Y23 and Y333 in response to stromal signals HGF and IGF-1, respectively, and IGF-1 expression was regulated by the Sonic Hedgehog (Shh) pathway. Both Shh and HGF were heterogeneously expressed in PDAC stroma, and only dual inhibition of these pathways could significantly suppress AnxA2 phosphorylation, PDAC growth, and metastasis. Taken together, our results illuminate tumor-stromal interactions, which drive metastasis, and provide a mechanism-based rationale for a stroma-directed therapy for PDAC. Cancer Res; 77(1); 41-52. ©2016 AACR.
了解基质信号如何调节胰腺导管腺癌（PDAC）的发展，可能会为该疾病提出新的治疗干预措施。在本研究中，我们评估了在PDAC微环境中被认为很重要的基质信号的转移作用。Src和IGF-1R分别响应基质信号HGF和IGF-1，使促转移分子膜联蛋白A2（AnxA2）在Y23和Y333位点发生磷酸化，并且IGF-1的表达受音猬因子（Shh）信号通路调控。Shh和HGF在PDAC基质中均呈异质性表达，只有对这些信号通路进行双重抑制才能显著抑制AnxA2磷酸化、PDAC生长和转移。综上所述，我们的结果阐明了驱动转移的肿瘤-基质相互作用，并为针对PDAC的基质导向治疗提供了基于机制的理论依据。《癌症研究》；77(1)；41 - 52。©2016美国癌症研究协会。
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