Integrin alpha3 expression as a prognostic factor in colon cancer: association with MRP-1/CD9 and KAI1/CD82.

Abstract

Recently, we established that a murine monoclonal antibody (MAb) MH8-4 inhibits the motility of the colon cancer cell line RPMI4788 and that it recognizes integrin alpha3. In addition, we have also cloned the motility-related protein-1 (MRP-1)/cluster of differentiation 9 (CD9) as a metastasis suppressor molecule. We investigated integrin alpha3 expression in 114 resected colon cancers using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to evaluate whether these experimental results are of relevance in the prognosis of actual colon cancers. Furthermore, we investigated the correlation of integrin alpha3 with MRP-1/CD9 and KAI1/CD82. Sixty patients (52.6%) were evaluated as integrin alpha3-positive and 54 patients (47.4%) as integrin alpha3-negative. Integrin alpha3 expression was associated with tumor status, lymph node status and pathologic stage. The overall and disease-free survival rates for patients whose tumors were positive for integrin alpha3 were significantly higher than for those with integrin alpha3-negative tumors (p < 0.001 and p < 0.001, respectively). This same tendency was observed in node-negative patients (p = 0.007 and p = 0.001, respectively). Integrin alpha3 was found to be the significant prognostic factor in a multivariate analysis using the Cox proportional hazards model (p = 0.036). A correlation was found between integrin alpha3 with MRP-1/CD9 and KAI1/CD82 for stage I tumors. However, no correlation was found in stage III tumors. Our data seem to suggest that low expression of integrin alpha3 is a useful indicator of a poor prognosis for colon cancer patients and that colon cancer progresses following collapse of the complex formed by integrin alpha3 with MRP-1/CD9 and KAI1/CD82.

• Authors: Hiroki Hashida, Arimichi Takabayashi, Takahiro Tokuhara, Toshihiko Taki, Keiichi Kondo, Nobuoki Kohno, Yoshio Yamaoka, Masayuki Miyake
• Journal: International journal of cancer (Int J Cancer) Vol. 97 Issue 4 Pg. 518-25 (Feb 01 2002) ISSN: 0020-7136 [Print] United States
• PMID: 11802216 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Antigens, CD
• Biomarkers, Tumor
• CD82 protein, human
• CD9 protein, human
• Integrin alpha3
• Integrins
• Kangai-1 Protein
• Macromolecular Substances
• Membrane Glycoproteins
• Neoplasm Proteins
• Proto-Oncogene Proteins
• RNA, Messenger
• RNA, Neoplasm
• Tetraspanin 29

Topics

• Adenocarcinoma (genetics, metabolism, mortality, pathology)
• Adult
• Aged
• Antigens, CD (biosynthesis, genetics, metabolism)
• Biomarkers, Tumor (biosynthesis, genetics)
• Cell Adhesion
• Cell Movement
• Colonic Neoplasms (genetics, metabolism, mortality, pathology)
• Disease Progression
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Integrin alpha3
• Integrins (biosynthesis, genetics)
• Kangai-1 Protein
• Macromolecular Substances
• Male
• Membrane Glycoproteins (metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Proteins (biosynthesis, genetics)
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Proto-Oncogene Proteins
• RNA, Messenger (biosynthesis)
• RNA, Neoplasm (biosynthesis)
• Retrospective Studies
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Analysis
• Tetraspanin 29