阴茎癌是罕见男性生殖系统肿瘤，淋巴结状态是决定患者治疗及预后关键因素。缺乏细胞株限制了阴茎癌转移分子机制的研究。我们建立了5株具有不同生物学特性的阴茎癌细胞株，采用Transwell浸润法连续筛选获得了转移潜能由低到高的细胞亚株，通过比较表达谱分析发现TSPAN18是可能的候选转移相关基因，在癌旁正常组织、配对原发灶和淋巴结转移灶中TSPAN18表达水平依次升高；预实验结果显示敲降TSPAN18可抑制阴茎癌细胞转移，而TSPAN18可能参与激活NF-kB信号通路。因此推测TSPAN18通过激活NF-kB通路促进阴茎癌淋巴结转移。本项目拟在分子、细胞、动物水平及临床标本多层面对TSPAN18的功能进行深入研究，阐明其调控NF-kB通路和下游靶基因的具体分子机制，阐明TSPAN18在阴茎癌淋巴结转移中的重要作用，并探讨TSPAN18作为阴茎癌淋巴结转移早期转移的诊断标志物和治疗靶点的可能性。

Penile squamous cell carcinoma (PeSCC) is a rare tumor in the male reproductive system. The status of lymph node is the hallmark that correlates with treatment and prognosis. The lack of cell line model limits the study of molecular mechanisms underlying PeSCC metastasis. We previously established five PeSCC cell lines, and developed a series of cell sub-lines with different metastatic potential from low to high through continuous transwell invasion screening. mRNA microarray analysis showed that TSPAN18 was likely a metastasis-related gene candidate, as the mRNA levels of TSPAN18 gradually increase in adjacent normal tissue, paired primary lesions and lymph node metastases. Our primary investigations showed that knocking down of TSPAN18 can suppress the migration of PeSCC cells, and TSPAN18 was closely correlated with the activation of NF-kB pathway. Thus, we speculate that TSPAN18 likely promotes lymph node metastasis in PeSCC via activating NF-kB pathway. In this proposal, we planned to study the function and mechanisms of TSPAN18 in PeSCC in levels of molecular biology, cell biology, nude mice and clinical analyses, and then to clarify the molecular mechanisms how TSPAN18 regulates NF-kB pathway and its downstream target genes, elucidate the important role of TSPAN18 in lymph node metastasis of PeSCC, and explore the possibility of TSPAN18 as a diagnostic marker and therapeutic target for early metastasis of lymph node in penile carcinoma.