ADHESION RECEPTORS IN ORAL CANCER INVASION AND GROWTH

生长和侵袭失调是口腔鳞状细胞癌（SCC）的特征。SCC侵入邻近组织需要整合素介导的细胞通过潜在的细胞外基质迁移。在癌细胞主动侵袭之前，它们必须启动对潜在细胞外基质的新生附着，并脱离其广泛的连接粘附。正常粘膜上皮的增殖仅限于基底角化细胞，与之相反，基底上口腔SCC细胞已经失去了对细胞外基质的锚定需求，并且在没有基底膜粘连的情况下继续不受控制地增殖。本研究的长期目标是明确粘附在调节口腔鳞状细胞侵袭、存活和生长中的重要性。在本提案中，将解决三个具体目标：1)鉴定特异性整合素配体对，诱导细胞间粘附解偶联并刺激细胞运动。2)确定口腔SCC细胞粘附的破坏是否会调节不依赖锚定的存活和生长。实验将利用人类口腔SCC细胞系和核心B中提供的动物，其组织病理学将在核心c中进行。项目计划与整合素粘附和细胞生长有关的广泛相互作用。拟议的研究将确定特定受体家族是否产生调节运动，生存和生长的代偿信号。这一信息将有助于扩大我们对粘附在控制口腔癌侵袭和肿瘤内增殖中的分子作用的理解。

Dysregulated growth and invasion characterize oral squamous cell carcinoma (SCC). SCC invasion into adjacent tissue requires integrin- mediated cell migration through the underlying extracellular matrix. Before they actively invade, the carcinoma cells must initiate nascent attachments to the underlying extracellular matrix and disengage their extensive junctional adhesions. In contrast to normal mucosal epithelium, where proliferation is restricted to basal keratinocytes, suprabasal oral SCC cells have lost their requirement for anchorage to extracellular matrix and continue to proliferate uncontrollably in the absence of basement membrane adhesions. The long-term goal of the proposed research is to define the importance of adhesion in regulating invasion, survival and growth in oral SCC cells. In this proposal three specific aims will be addressed: 1) Identify specific integrin-ligand pairs that induce uncoupling of intercellular adhesion and stimulate cell motility. 2) Determine whether disruption of oral SCC cell adhesion will modulate anchorage-independent survival and growth. The experiments will utilize human oral SCC cell lines and the animal provided in Core B with histopathology to be performed in Core C. Extensive interactions related to integrin adhesion and cell growth are planned with Project. The proposed studies will establish whether specific receptor families generate compensatory signals that regulate motility, survival and growth. This information will help expand our understanding, at the molecular, of the role of adhesion in controlling unregulated invasion and intratumoral proliferation of oral cancer.