HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment.
HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment.
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DOI：
10.1158/1078-0432.ccr-16-0951
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发表时间：
2016-08-15
期刊：
影响因子：
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通讯作者：
Grandis JR
中科院分区：
文献类型：
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作者：
Hartmann S;Bhola NE;Grandis JR
迄今为止的研究已经揭示了几个主要的分子改变，有助于头颈部鳞状细胞癌（HNSCC）的开始，进展，转移扩散和治疗失败。EGFR是FDA批准的唯一治疗靶点，但对西妥昔单抗的反应有限。细胞受体的激活和串扰以及随后不同信号传导途径的激活有助于限制单一途径的阻断活性。肝细胞生长因子（HGF）受体，Met，已牵连在HNSCC肿瘤发生和EGFR抑制剂耐药性。HGF是Met的唯一配体，在肿瘤微环境中过表达。已经在HNSCC中研究了HGF/Met信号传导在增殖、转移和血管生成中的作用，从而导致使用各种Met抑制剂和HGF抗体的临床试验。然而，HGF/Met信号传导轴在介导肿瘤微环境中的作用在HNSCC中相对研究不足。在这篇综述中，我们讨论了Met和HGF在HNSCC中的功能作用，重点是肿瘤微环境和免疫系统。
Studies to date have revealed several major molecular alterations that contribute to head and neck squamous cell carcinoma (HNSCC) initiation, progression, metastatic spread, and therapeutic failure. The EGFR is the only FDA-approved therapeutic target, yet responses to cetuximab have been limited. Activation and cross-talk of cellular receptors and consequent activation of different signaling pathways contribute to limited activity of blockade of a single pathway. The hepatocyte growth factor (HGF) receptor, Met, has been implicated in HNSCC tumorigenesis and EGFR inhibitor resistance. HGF, the sole ligand of Met, is overexpressed in the tumor microenvironment. The role of HGF/Met signaling in proliferation, metastasis, and angiogenesis has been investigated in HNSCC, leading to clinical trials with various Met inhibitors and HGF antibodies. However, the role of the HGF/Met signaling axis in mediating the tumor microenvironment has been relatively understudied in HNSCC. In this review, we discuss the functional roles of Met and HGF in HNSCC with a focus on the tumor microenvironment and the immune system.