ADHESION RECEPTORS IN ORAL CANCER INVASION AND GROWTH

口腔鳞状细胞癌(SCC)的特点是生长和侵袭失调。鳞状细胞癌侵袭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。癌细胞在主动侵袭之前，必须启动与潜在细胞外基质的新生附着，并解除其广泛的连接粘连。与正常黏膜上皮细胞仅限于基底层角质形成细胞增殖不同，基底层以上口腔鳞状细胞癌细胞失去了对细胞外基质的锚定要求，在没有基底膜粘连的情况下继续不受控制地增殖。这项拟议研究的长期目标是确定黏附在调节口腔鳞癌细胞侵袭、存活和生长中的重要性。在这项建议中，将解决三个具体目标：1)确定特定的整合素-配体对，诱导细胞间黏附的解偶联并刺激细胞运动。2)确定口腔SCC细胞黏附的破坏是否会调节非黏附的生存和生长。这些实验将利用人类口腔鳞状细胞癌细胞系和Core B中提供的组织病理学动物，在Core C中进行。项目计划进行与整合素黏附和细胞生长相关的广泛互动。拟议中的研究将确定特定的受体家族是否会产生调节运动、生存和生长的代偿信号。这些信息将有助于在分子水平上扩大我们对黏附在控制口腔癌无调控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.