1999 Fiscal Year Final Research Report Summary

Implication of E-cadherin in Cancer Metastasis

Research Project

Project/Area Number	09671756
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Otorhinolaryngology
Research Institution	Wakayama Medical College
Principal Investigator	YODA Jun-ichi Wakayama Medical College, 医学部, 助手 (10230822)
Co-Investigator(Kenkyū-buntansha)	SAITO Tadahito Wakayama Medical College, 医学部, 講師 (80205658)
Project Period (FY)	1997 – 1999
Keywords	E-cadherin / cancer metastasis / invasion / angiogenesis
Research Abstract	Metastasis of malignant tumor cells is composed of highly complicated process. In the metastatic process, tumor cells never fail to penetrate into capillary vessels or lymphatic duct. This invasiveness is the most important character of highly metastatic tumor cells. E-cadherin is a calcium ion-dependent cell-cell adhesion molecule expressed mostly in epithelial tissue. E-cadherin-positive human carcinoma cell lines showed enhanced invasiveness after treatment of anti-E-cadherin antibody. It also related to increased invasiveness by releasing proteolytic enzymes such as matrix metalloproteinase-2 or -9 against extracellular matrix around tumor cells. It was considered that loss of normal E-cadherin function promoted invasiveness of carcinoma cells. The loss of cell-cell adhesion due to functional derangement of E-cadherin can be intiating step in the whole invasion process. Angiogenesis is required for expansion of metastatic colonies as well as tumor growth. Cell lines derived from head and neck cancer showed significant production of vascular endothelial growth factor (VEGF), a most common angiogenic factor, indicating that tumor cells induce angiogenesis for their own growth. We have investigated whether alterations in the cell-cell adhesion can trigger changes in the expression of the VEGF gene. These cells exhibited increased VEGF mRNA and protein after disruption of intercellular adhesion by anti-E-cadherin antibody treatment. We conclude that the function of E-cadherin is closely correlated with invasiveness and angiogenesis.