Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591736
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: YOSHINO Kiyoshi Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (90362730)
• Co-Investigator(Kenkyū-buntansha): ENOMOTO Takayuki Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90283754) ; FUJITA Masami Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (60303963)
• Project Period (FY): 2005 – 2006
• Keywords: cervical cancer / 3^<rd> chromosome / TSC403 / LAMP3 / metastasis / invasion

Research Abstract

LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2,were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis.
To clarify the metastatic potential of the LAMP3 in cervical cancers, we transfected a LAMP3-expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS-cell-injected mice and in only 1 of 11 control mice. Histological study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space.
In clinical samples, quantitative real-time RT-PCR analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias (CINs), compared to a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers.
These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential, and may be a prognostic factor for cervical cancer.

Research Products

• [Journal Article] Overexpression of LAMP3/TSC403/DC-LAMP Promotes Metastas is in Uterine Cervical Cancer (2005)
  • Author(s): Kanao H, Enomoto T, Kimura T, Fujita M, Nakashima R, Ueda Y, Ueno Y, Miyatake T, Yoshizaki T, Buzard G S, Tanigami A, Yoshino K, Murata Y
  • Journal Title: Cancer Res 65(19) Pages: 8640-8645
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of Lamp3/TSC403/DC-LAMP Promotes Metastasis in Uterine Cervical Cancer (2005)
  • Author(s): Kanao H, Enomoto T, Kimura T, Fujita M, Nakashima R, Ueda Y, Ueno Y, Miyatake T, Yoshizaki T, Buzard G S, Tanigami A, Yoshino K, Murata Y
  • Journal Title: Cancer Res,2005 65(19) Pages: 8640-8645
  • Description: 「研究成果報告書概要(欧文)」より