ADHESION RECEPTORS IN ORAL CANCER INVASION AND GROWTH

口腔鳞状细胞癌（SCC）的特征是生长和侵袭失调。鳞状细胞癌侵入邻近组织需要整合素介导的细胞迁移通过下面的细胞外基质.癌细胞在主动侵入之前，必须启动与下层细胞外基质的新生附着，并脱离其广泛的连接粘连。与增殖仅限于基底角化细胞的正常粘膜上皮相反，基底上口腔SCC细胞已经失去了锚定细胞外基质的要求，并且在没有基底膜粘附的情况下继续不受控制地增殖。这项研究的长期目标是确定粘附在调节口腔SCC细胞侵袭、存活和生长中的重要性。在该提案中，将解决三个具体目标：1）识别诱导细胞间粘附解偶联并刺激细胞运动的特定整合素-配体对。2)确定口腔鳞状细胞癌细胞粘附的破坏是否会调节锚定非依赖性生存和生长。实验将使用人口腔SCC细胞系和核心B中提供的动物，并在核心C中进行组织病理学检查。与项目计划了与整合素粘附和细胞生长相关的广泛相互作用。拟议的研究将确定特定受体家族是否产生调节运动、存活和生长的补偿信号。这些信息将有助于扩大我们从分子水平上对粘附在控制口腔癌不受调节的侵袭和瘤内增殖中的作用的理解。

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.