ADHESION AND PROLIFERATION IN ORAL CANCER PROGRESSION

口腔癌的特点是不断生长和侵袭，经常导致远处转移。虽然在定义癌症的临床和组织病理学特征方面取得了重大进展，但肿瘤进展的分子机制仍然知之甚少。该计划的主要重点是进一步确定在正常粘膜逐步转化为口腔异型增生，并最终转化为浸润性鳞状细胞癌过程中发生的变化。该项目包括加州旧金山弗朗西斯科的四个互动研究实验室。在肿瘤标志物分析、生长因子和粘附受体功能、信号转导和分子遗传学等方面有丰富的经验。此外，该小组已经启动了与表征肿瘤进展的顺序过程相关的复杂问题的分析方法。项目I阐述了肿瘤发生过程中TGF-α加工的机制及其通过细胞内信号通路的调节。项目II将研究α v类整合素受体在调节细胞生长和侵袭中的重要性，α v类整合素受体结合细胞外基质配体以及TGF-β的潜在形式。项目III将明确特定细胞粘附系统在调节正常和恶性口腔角质形成细胞的存活、凋亡和生长中的重要性。项目IV将分析人乳头瘤病毒和MRP-8/14在口腔癌发病机制中的作用。此外，该计划将支持年轻研究人员在肿瘤内寻找种子，提出口腔癌基础和临床研究项目。这两个初步试点项目将研究（1）p14/ARF状态作为口腔癌发展的分子预测因子，以及（2）纤连蛋白及其受体在调节口腔鳞状细胞癌侵袭和生长中的作用。这些互动式研究和可行性项目将得到行政核心、细胞培养/动物模型核心和组织病理学核心的支持。新成立的UCSF综合癌症中心的专业核心将提供额外的基础设施支持。

Oral cancer is characterized by relentless growth and invasion, frequently resulting in distant metastasis. While significant progress has been made in defining the clinical and histopathological characteristics of cancer, the molecular mechanisms of tumor progression remain poorly understood. The major focus of the proposed Program Project is to further define the alterations that occur during the stepwise conversion of normal mucosa to oral dysplasia, and finally to invasive squamous cell carcinoma. The project comprises four interactive research laboratories at the University of California San Francisco. That have considerable experience in defining molecules related to tumor progression, including tumor marked analysis, growth factor and adhesion receptor function, signal transduction, and molecular genetics. Moreover, this group has already initiated approaches to the analysis of the complex issues related to the sequential processes characterizing tumor progression. Project I addresses the mechanism of TGF-alpha processing and its regulation by intracellular signaling pathways during carcinoma development. Project II will examine the importance of he alphav class of integrin receptors, which bind extracellular matrix ligands as well as the latent form of TGF- beta, in regulating cell growth and invasion. Project III will define the importance of specific cell adhesion systems in regulating survival, apoptosis and growth in normal and malignant oral keratinocytes. Project IV will analyze the role of human papillomavirus and MRP-8/14 in oral cancer pathogenesis. In addition, the Program will support intratumoral seed finding of young investigators proposing basic and clinical research projects in oral cancer. The two initial pilot projects will examine (1) p14/ARF status as a molecular predictor of oral cancer development, and (2) the role of fibronectin and its receptors in regulating invasion and growth of oral squamous cell carcinoma. These interactive research and feasibility projects will be supported by an administrative core, a cell culture/animal model core, and a histopathology core. Additional infrastructure support will be provided by the specialized cores of the newly established UCSF Comprehensive Cancer Center.