Gene Therapy for Inhibition of Metastasis in Human Prostate

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10671495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Teikyo University
• Principal Investigator: SATO Naohide Teikyo University School of Medicine, Lecturer, 医学部, 講師 (50287017)
• Project Period (FY): 1998 – 1999
• Keywords: prostate cancer / metastasis / gene therapy

Research Abstract

INTRODUCTION & OBJECTIVES : KAI 1 gene was recently identified as a metastatic suppressor gene for rat prostate cancer and turned out CD82, transmembrane 4 superfamily. This study was undertaken to clarify the role of KAI 1 gene in the process of metastasis of human prostate cancer and to examine the usefulness of gene therapy by using KAI 1 cDNA. MATERIAL, METHODS & RESULTS : Androgen-sensitive human prostate cancer cell line LNCaP cells (lack KAI 1 expression) were transfected with KAI 1 expression plasmid DNA. Several stable transfectants were isolated and designated LN-K cells. Expressions of KAI 1 gene were confirmed by Northern blots and immunohistochemistry. There was no significant difference in proliferation and androgen-sensitivity between original LNCaP (LN-O), mock transfected-LNCaP (LN-M) and LN-K cells in vitro. An in vitro invasion assay revealed that invasion activity in LN-K cells was extremely lower than that in LN-O and LN-M cells (p<0.01). LN-O, LN-M and LN-K cells were separately injected into dorsal prostate of male SCID mouse. They were sacrificed when their serum levels of prostate specific antigen reached 100 ng/ml, and prostate, pelvic lymph nodes, lungs, liver, kidneys and vertebral bones were histologically examined. In LN-O (n=20) and LN-M (n=19) cells-injected mice, prostate tumor was identified in about 75% of mice, and pelvic lymph nodes and pulmonary metastasis were found in about 75% and 25%, respectively. In contrast, prostate tumor was identified in 20% of mice, and no metastasis was identified in LN-K cells-injected mice (n=38).
CONCLUSIONS : Expression of KAI 1 gene completely suppressed metastatic ability of LNCaP human prostate cancer cells in vivo, probably due to inhibition of invasive ability. Moreover, KAI 1 gene products may inhibit tumor growth in the prostate. Transrectal introduction of KAI 1 gene into organ-confined prostate cancer may be one possible option of gene therapy to control further growth and metastasis.