The role of lymphangiogenetic growth factor and chemokine receptor in lymph nodes metastasis of oral squamous cell carcinoma

淋巴结转移是口腔鳞状细胞癌预后不良的最决定性因素。提示癌细胞促进淋巴管生成，癌细胞表达的趋化因子受体在淋巴结转移中起重要作用。在本研究中，我们研究了CXCR4（基质细胞衍生因子趋化因子受体[SDF]-1； CXCL12）是否在口腔鳞状细胞癌中表达。对活检或手术标本进行免疫组化染色。几乎在所有的病例中都检测到CXCR4的表达，并且定位于癌细胞的膜和细胞质中。转移性肿瘤细胞在淋巴结中的表达强于原发组织。用D2-40抗体免疫染色评估肿瘤内淋巴管密度（LVD）。然而，LVD与CXCR4表达无相关性。在本实验室维持的口腔鳞癌细胞中，CXCR4 mRNA和蛋白仅在HSO-2、KB和SCC25细胞中表达，未发现CXCR4和SDF-1同时表达。此外，为了建立裸鼠淋巴结转移的有效模型，我们将5种表达CXCR4的细胞原位接种于足垫或足垫。虽然KB/COX-2细胞表达CXCR4多于对照KB/Neo细胞，但CXCR4并没有提高局部淋巴结转移率。

Lymph node metastasis is the most determining factor of a poor prognosis for oral squamous cell carsinoma. It is suggested that cancer cells promote lymphangiogenesis and that chemokine receptors expressed by cancer cells play an important role in lymph node metastasis.In this study, we investigated whether CXCR4 (chemokine receptor for stromal cell derived factor[SDF]-1; CXCL12) is expressed in oral squamous cell carcinoma. Immunohistochemical stainings of the specimens obtained from biopsy or operation were performed. CXCR4 expression was detected in almost all cases tested and was localized in the membrane and cytoplasm of the cancer cells. Metastatic tumor cells in lymph nodes had stronger expression than in the primary tissue. Lymphatic vessel density (LVD) was evaluated within the tumor by immunostaining with a D2-40 antidody. However, there was no correlation between LVD and CXCR4 expression.CXCR4 mRNA and protein were expressesd only in HSO-2, KB and SCC25 cells among oral squamous carcinoma cells maintained in our laboratory, but co-expression of both CXCR4 and SDF-1 was not shown. Furthermore, in order to establish the useful model of lymph nodes metastasis in nude mice, we inoculated 5 kinds of cells expressing CXCR4 orthotopically or to foot-pad. Although KB/COX-2 cells expressed CXCR4 more than control KB/Neo cells, CXCR4 did not enhance the rate of regional lymph nodes metastasis.