Possibility of GVT effects on oral malignant nepolasms

Research Project

Project/Area Number	13671977
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	病態科学系歯学(含放射線系歯学)
Research Institution	Fukuoka Dental College
Principal Investigator	OHNO Jun Fukuoka Dental College, Lecturer, 歯学部, 講師 (10152208)
Project Period (FY)	2001 – 2003
Project Status	Completed (Fiscal Year 2003)
Budget Amount *help	¥2,700,000 (Direct Cost: ¥2,700,000) Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000) Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000) Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords	GVHD / GVT / cytokines / CTL / immunohistochemistry / malignant melanoma / metastasis / tumor immunology / sialyltrasferase / 糖タンパク / シアル酸 / 細胞障害性T細胞 / マウス / ラット / 病理組織学
Research Abstract	The results obtained were divided into three parts ; 1) effects of MCP-1 producing macrophages on the development of local GVH reactions in the oral mucosa, 2) GVT effects on oral melanoma in mice, and 3) biosynthesis of sialic acid on the terminal portion of glycoconjugates can affect effects of GVT against oral melanoma in mice. First, in local GVH reaction of the oral mucosa, macrophages infiltrate into the upper region of lamina propria after an expression of ICAM-1 in epithelial cells. We suggest that MCP-1, produced by macrophages, may be responsible for the chemotactic factor of CTL into surface epithelia of the oral mucosa. Second, GVT effects may depend on degree of systemic GVH reaction. In advanced stages of systemic GVHD, CTL infiltrated directly into nests of melanoma cells (B16 ; C57BL/6-origin), whereas less infiltration of CTL was noted in the early phase. We suggested that GVT effects were induced by immunological pathway of acute oral mucosal GVHD. However, CTL reaction against tumor cells were not specific, because they also attacked oral mucosa, ispecially epithelial cells. Third, the cell surface glycoconjugates of melanoma cells injected were modified during their development in the oral mucosa. We examined histochemically an attachment of sialic acid on the terminal portion of glycoconjugates in melanoma cells. Binding of sialic acid on the cell surface may responsible for susceptibleness of metastasis into submandibular lymph nodes and for difficulties of GVT effects.