Role of the implantation-related cell adhesion molecule, trophinin in progression of colorectal cancer.

• Project/Area Number: 15390115
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Shinshu University
• Principal Investigator: NAKAYAMA Jun Shinshu University, Graduate School of Medicine, Pathology, Professor, 大学院・医学研究科, 教授 (10221459)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥13,700,000 (Direct Cost: ¥13,700,000); Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000); Fiscal Year 2003: ¥5,600,000 (Direct Cost: ¥5,600,000)
• Keywords: cell adhesion molecule / implantation / colorectal cancer / invasiveness / immunohistochemistry / cDNA microarray / 大腸 / ホルモン / 転移 / 胚細胞腫瘍 / 転位

Research Abstract

Trophinin is a cell adhesion molecule expressed by both trophoblasts and maternal cells, where it is implicated in human embryo implantation through a homophilic mechanism. During the process of implantation, trophoblasts aggressively invade and actively proliferate to form the placenta, a process resembling tumor invasion. In the research project, we first identify human chorionic gonadotrophin (hCG) as a stimulator of trophinin, We then demonstrate that trophinin is expressed in colorectal cancer cells in 59.5% of 42 patients examined, and that its expression is closely associated with poor prognosis. Expression of human chorionic gonadotrophin was associated with trophinin expression in these patients. To determine whether trophinin enhances invasion of cancer cells, colon adenocarcinoma SW480-tro cells stably expressing trophinin were established by transfection, and Matrigel assays showed that these cells were more invasive than mock-transfected cells. A microarray search for transcripts up-regulated in SW480 cells transiently transfected by trophinin cDNA identified the high-mobility group box 1 gene (HMGB1). In addition, the receptor for advanced glycation end products (RAGE), which serves as a ligand of HMGB1, was largely co-expressed with trophinin in colorectal cancer tissue specimens. These results suggest that trophinin enhances cancer cell invasiveness through a mechanism involving HMGB1/RAGE and that its expression indicates a poor prognosis in colorectal cancer.

Research Products

• [Journal Article] Female adnexal tumor of probable wolffian origin : A morphological, immunohistochemical, and ultrastructural study with c-kit gene analysis (2006)
  • Author(s): Harada O, et al.
  • Journal Title: Pathology International 56・2 Pages: 95-100
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance (2006)
  • Author(s): Omachi T, et al.
  • Journal Title: Cancer Letters (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hypermethylation of ASC/TMSl is a sputum marker for late-stage lung cancer (2006)
  • Author(s): Ota Machida E, et al.
  • Journal Title: Cancer Research (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Female adnexal tumor of probable wolffian origin : A morphological, immunohistochemical, and ultrastructural study with c-kit gene analysis (2006)
  • Author(s): Harada O, Ota H, Takagi K, Matsuura H, Hidaka E, Nakayama J
  • Journal Title: Pathol Int 56 Pages: 95-100
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Female adnexal tumor of probable wolffian origin : Morphological, immunohistochemical, and ultrastructural study with c-kit gene analysis. (2006)
  • Author(s): Harada, O. et al.
  • Journal Title: Pathology International 56・2 Pages: 95-100
• [Journal Article] Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance (2006)
  • Author(s): Omachi, T. et al.
  • Journal Title: Cancer Letters (In press)
• [Journal Article] Malignant myoepithelioma (myoepithelial carcinoma) of soft tissue (2005)
  • Author(s): Harada O, et al.
  • Journal Title: Pathology International 55・8 Pages: 510-513
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of core 2 β1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression (2005)
  • Author(s): Hagisawa S, et al.
  • Journal Title: Glycobiology 15・10 Pages: 1016-1024
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Malignant myoepithelioma (myoepithelial carcinoma) of soft tissue. (2005)
  • Author(s): Harada O, Ota H, Nakayama J
  • Journal Title: Pathol Int 55 Pages: 510-513
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of core 2 β1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression (2005)
  • Author(s): Hagisawa S, Ohyama C, Takahashi T, Endoh M, Moriya T, Nakayama J, Arai Y, Fukuda M
  • Journal Title: Glycobiology 15 Pages: 1016-1024
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Malignant myoepithelioma (myoepithelial carcinoma) of soft tissue (2005)
  • Author(s): Harada, O. et al.
  • Journal Title: Pathology International 55・8 Pages: 510-513
• [Journal Article] Expression of core2 β1,6-N-acetylglucosaminyltransferase facilitates prestate cancer progression (2005)
  • Author(s): Hagisawa, S. et al.
  • Journal Title: Glycobiology 15・10 Pages: 1016-1024
• [Journal Article] Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor (2004)
  • Author(s): Hatakeyama S, et al.
  • Journal Title: Cancer Research 64・12 Pages: 4257-4264
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor (2004)
  • Author(s): Hatakeyama S, Ohyama C, Minagawa S, Inoue T, Kakinuma H, Kyan A, Arai Y, Suga T, Nakayama J, Kato T, Habuchi T, Fukuda MN
  • Journal Title: Cancer Res 64 Pages: 4257-4262
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor. (2004)
  • Author(s): Hatakeyama S, et al.
  • Journal Title: Cancer Research 64・12 Pages: 457-4262
• [Journal Article] Implantation-dependent expression of trophinin by maternal Fallopian tube epithelia during tubal pregnancies : Possible role of human chorionic gonadotrophin on ectopic pregnancy (2003)
  • Author(s): Nakayama J, et al.
  • Journal Title: American Journal of Pathology 163・12 Pages: 2211-2219
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Implantation-dependent expression of trophinin by maternal Fallopian tube epithelia during tubal pregnancies : Possible role of human chorionic gonadotrophin on ectopic pregnancy (2003)
  • Author(s): Nakayama J, Aoki D, Suga T, Akama TO, Ishizone S, Yamaguchi H, Imakawa K, Nadano D, Fazleabas AT, Katsuyama T, Nozawa S, Fukuda MN
  • Journal Title: Am J Pathol 163 Pages: 2211-2219
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Immunohistochemical demonstration of proliferating lymphatic vessels in colorectal carcinoma and its clinicopathological significance
  • Author(s): Omachi T, Kawai Y, Mizuno R, Nomiyama T, Miyagawa S, Ohhashi T, Nakayama J
  • Journal Title: Cancer Lett (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer
  • Author(s): Ota Machida E, Brock MV, Hooker C, Nakayama J, Ishida A, Amano J, Picchi MA, Belinsky SA, Herman JG, Taniguchi S, Baylin SB
  • Journal Title: Cancer Res (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nakayama J, et al.: "Implantation -dependent expression of trophinin by maternal Fallopian tube epithelia during tubal pregnancies : Possible role of human chorionic gonadotrophin on ectopic pregnancy"American Journal of Pathology. 163・12. 2211-2219 (2003)