Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, Veterans Affairs Medical Center, San Francisco, California, USA.
Head Neck. 2013 Apr;35(4):511-20. doi: 10.1002/hed.22991. Epub 2012 Mar 31.
CD44 is a transmembrane receptor found on many different benign and malignant cells. Hyaluronan (HA), a major component of the extracellular matrix, is the primary ligand for CD44 receptors. In cancer cells, HA interaction with CD44 promotes multiple signaling pathways that influence tumor cell progression behaviors in a variety of solid tumors. Increasing evidence indicates that HA and CD44 signaling play an important role in oral cavity squamous cell carcinoma progression. HA is primarily synthesized by hyaluronan synthases, and the current study investigated the role of hyaluronan synthase 2 (HAS 2) in oral cavity carcinoma progression behaviors.
Analysis of HAS 2 mRNA and protein expression, HA production, and HAS 2-mediated tumor cell proliferation and migration behaviors with and without HAS 2 suppression were carried out on 2 established oral cavity cancer cell lines. Immunohistochemical analysis of HAS 2 and CD44 expression in oral cavity carcinoma tumor specimens was performed.
HAS 2 was expressed in the 2 oral cancer cell lines, HSC-3 and SCC-4. Suppression of HAS 2 expression resulted in CD44-dependent decreased tumor cell migration, decreased tumor cell growth, and increased cisplatin sensitivity, suggesting the importance of tumor cell HA production to promote in vitro tumor progression behaviors in oral cancer cells. Increased HAS 2 expression in oral cavity carcinoma clinical specimens was associated with poor clinicopathologic characteristics and worse disease-free survival.
HAS 2 may be a potential therapeutic target for the treatment of oral cavity cancer.
CD44 是一种存在于许多良性和恶性细胞表面的跨膜受体。透明质酸（HA）是细胞外基质的主要成分，是 CD44 受体的主要配体。在癌细胞中，HA 与 CD44 的相互作用促进了多种信号通路，这些信号通路影响多种实体瘤中肿瘤细胞的进展行为。越来越多的证据表明，HA 和 CD44 信号在口腔鳞状细胞癌的进展中发挥着重要作用。HA 主要由透明质酸合酶合成，本研究探讨了透明质酸合酶 2（HAS 2）在口腔癌进展行为中的作用。
在 2 种已建立的口腔癌细胞系中，分析 HAS 2 mRNA 和蛋白表达、HA 产生以及 HAS 2 介导的肿瘤细胞增殖和迁移行为，并进行 HAS 2 抑制。对口腔癌肿瘤标本进行 HAS 2 和 CD44 表达的免疫组织化学分析。
HAS 2 在 2 种口腔癌细胞系 HSC-3 和 SCC-4 中表达。抑制 HAS 2 表达导致 CD44 依赖性肿瘤细胞迁移减少、肿瘤细胞生长减少和顺铂敏感性增加，表明肿瘤细胞 HA 产生对促进口腔癌细胞体外肿瘤进展行为的重要性。口腔癌临床标本中 HAS 2 表达增加与较差的临床病理特征和较差的无病生存率相关。
HAS 2 可能是治疗口腔癌的潜在治疗靶点。
