Surgery Today

, Volume 28, Issue 10, pp 1001–1006 | Cite as

Separate functions of α2β1 and α2β1 integrins in the metastatic process of human gastric carcinomaintegrins in the metastatic process of human gastric carcinoma

  • Hideki Ura
  • Ryuichi Denno
  • Koichi Hirata
  • Koji Yamaguchi
  • Takahiro Yasoshima
Original Articles


The expression of α2β1 and α3β1 integrins was studied immunohistochemically in 110 resected human gastric carcinomas. Formalin-fixed and paraffin-embedded samples were serially sectioned and stained with monoclonal antibodies specifically against the α2 and α3 subunits of β1 integrins. Approximately 27% of the tumors expressed α3β1 integrin, and 20% expressed α3β1 integrin. The expression of α3β1 integrin was associated with lymph node and liver metastases (P<0.05 andP<0.05, respectively), and the expression of α3β1 integrin was associated with liver and peritoneal metastases (P<0.005 andP<0.0005, respectively). A multivariate analysis by the logistic regression model revealed that the expression of α3β1 and/or α3β1 integrins was an independent factor related to liver metastasis, and that the expression of α3β1 integrin was as strong an influence on the formation of peritoneal metastases as the depth of invasion. The expression of α3β1 integrin also correlated with increased invasiveness of the tumor; however, there was no correlation between α2β1 integrin expression and the invasiveness. These results suggest that α2β1 and α3β1 integrins have separate influences on the metastatic properties of cancer cells.

Key Words

α2β1 integrin α3β1 integrin metastasis gastric carcinoma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Liotta LA, Rao CN, Wewer UM (1986) Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem 55:1037–1057CrossRefPubMedGoogle Scholar
  2. 2.
    Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554CrossRefPubMedGoogle Scholar
  3. 3.
    Akiyama SK, Yamada KM (1987) Biosynthesis and acquisition of biological activity of the fibronectin receptor. J Biol Chem 262:17536–17592PubMedGoogle Scholar
  4. 4.
    Hemler ME (1990) VLA proteins in the integrin family: structures, functions and their role on leukocytes. Annu Rev Immunol 8:365–400CrossRefPubMedGoogle Scholar
  5. 5.
    Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25CrossRefPubMedGoogle Scholar
  6. 6.
    Chan BMC, Matsuura N, Takada Y, Zetter BR, Hemler ME (1990) In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science 251:1600–1602CrossRefGoogle Scholar
  7. 7.
    Tawil NJ, Gowri V, Djoneidi M, Nip J, Carbonetto S, Brodt P (1996) Integrin α3β1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma. Int J Cancer 66:703–710CrossRefPubMedGoogle Scholar
  8. 8.
    Japanese Research Society for Gastric Cancer (1995) In: Nishi M, Omori Y, Miwa K (eds) Japanese classification of gastric carcinoma, 1st edn. Kanehara, TokyoGoogle Scholar
  9. 9.
    Wakita K, Kohno N, Sakoda Y, Ishikawa Y, Sakaue M (1996) Decreased expression of the DCC gene in human breast carcinoma. Surg Today 26:900–903CrossRefPubMedGoogle Scholar
  10. 10.
    Fujita S, Suzuki H, Kinoshita M, Hirohashi S (1992) Inhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin β1 subunit antibody. Jpn J Cancer Res 83:1317–1326PubMedGoogle Scholar
  11. 11.
    Yamada KM, Kennedy DW, Yamada SS, Gralnick H, Chen WT, Akiyama SK (1990) Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration. Cancer Res 50:4485–4496PubMedGoogle Scholar
  12. 12.
    Giancotti FG, Rouslahti E (1990) Elevated levels of the α3β1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell 60:849–859CrossRefPubMedGoogle Scholar
  13. 13.
    Schreiner C, Fisher M, Hussein S, Juliano RL (1991) Increased tumorigenicity of fibronectin receptor deficient Chinese hamster ovary cell variants. Cancer Res 51:1738–1740PubMedGoogle Scholar
  14. 14.
    Natali PG, Nicotra MR, Bartolazzi A, Cavaliere R, Bigotti A (1993) Integrin expression in cutaneous malignant melanoma: association of the α31 heterodimer with tumor progression. Int J Cancer 54:68–72CrossRefPubMedGoogle Scholar
  15. 15.
    Ignatis MJ, Reichardt LF (1988) Identification of a neural laminin receptor: an Mr 200/120 kd integrin heterodimer that binds laminin in a divalent cation-dependent manner. Neuron 1:715–725Google Scholar
  16. 16.
    Kramer RH, Marks N (1989) Identification of integrin collagen receptors of human melanoma cells. J Biol Chem 264:4684–4688PubMedGoogle Scholar
  17. 17.
    Wayner EA, Carter WG (1987) Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique α and common β subunits. J Cell Biol 105:1873–1884CrossRefPubMedGoogle Scholar
  18. 18.
    Carter WG, Ryan MC, Gahr PF (1991) Epiligrin, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes. Cell 65:599–610CrossRefPubMedGoogle Scholar
  19. 19.
    Weinel RJ, Rosendahl A, Neumann K, Chaloupka B, Erb D, Rothmund M, Santoso S (1992) Expression and function of α2, -α3, -α5 and -α6-integrin receptors in pancreatic carcinoma. Int J Cancer 52:827–833CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • Hideki Ura
    • 1
  • Ryuichi Denno
    • 1
  • Koichi Hirata
    • 1
  • Koji Yamaguchi
    • 1
  • Takahiro Yasoshima
    • 1
  1. 1.First Department of SurgerySapporo Medical University School of MedicineSapporoJapan

Personalised recommendations