The role of lymphangiogenetic growth factor and chemokine receptor in lymph nodes metastasis of oral squamous cell carcinoma

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17592122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hyogo College of Medicine
• Principal Investigator: KISHIMOTO Hiromitsu Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (30291818)
• Co-Investigator(Kenkyū-buntansha): URADE Masahiro Hyogo College of Medicine, Faculty of Medicine, Professor (70104883) ; SAKURAI Kazunari Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (30129118)
• Project Period (FY): 2005 – 2006
• Keywords: oral cancer / lymph node metastasis / chemokine / chemokine receptor / metastasis model / nude mouse / lymphangiogenesis / squamous cell carcinoma

Research Abstract

Lymph node metastasis is the most determining factor of a poor prognosis for oral squamous cell carsinoma. It is suggested that cancer cells promote lymphangiogenesis and that chemokine receptors expressed by cancer cells play an important role in lymph node metastasis.
In this study, we investigated whether CXCR4 (chemokine receptor for stromal cell derived factor[SDF]-1; CXCL12) is expressed in oral squamous cell carcinoma. Immunohistochemical stainings of the specimens obtained from biopsy or operation were performed. CXCR4 expression was detected in almost all cases tested and was localized in the membrane and cytoplasm of the cancer cells. Metastatic tumor cells in lymph nodes had stronger expression than in the primary tissue. Lymphatic vessel density (LVD) was evaluated within the tumor by immunostaining with a D2-40 antidody. However, there was no correlation between LVD and CXCR4 expression.
CXCR4 mRNA and protein were expressesd only in HSO-2, KB and SCC25 cells among oral squamous carcinoma cells maintained in our laboratory, but co-expression of both CXCR4 and SDF-1 was not shown. Furthermore, in order to establish the useful model of lymph nodes metastasis in nude mice, we inoculated 5 kinds of cells expressing CXCR4 orthotopically or to foot-pad. Although KB/COX-2 cells expressed CXCR4 more than control KB/Neo cells, CXCR4 did not enhance the rate of regional lymph nodes metastasis.