Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Liotta LA, Rao CN, Wewer UM (1986) Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem 55:1037–1057
Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554
Akiyama SK, Yamada KM (1987) Biosynthesis and acquisition of biological activity of the fibronectin receptor. J Biol Chem 262:17536–17592
Hemler ME (1990) VLA proteins in the integrin family: structures, functions and their role on leukocytes. Annu Rev Immunol 8:365–400
Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25
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 251:1600–1602
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 66:703–710
Japanese Research Society for Gastric Cancer (1995) In: Nishi M, Omori Y, Miwa K (eds) Japanese classification of gastric carcinoma, 1st edn. Kanehara, Tokyo
Wakita K, Kohno N, Sakoda Y, Ishikawa Y, Sakaue M (1996) Decreased expression of the DCC gene in human breast carcinoma. Surg Today 26:900–903
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 83:1317–1326
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 50:4485–4496
Giancotti FG, Rouslahti E (1990) Elevated levels of the α3β1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell 60:849–859
Schreiner C, Fisher M, Hussein S, Juliano RL (1991) Increased tumorigenicity of fibronectin receptor deficient Chinese hamster ovary cell variants. Cancer Res 51:1738–1740
Natali PG, Nicotra MR, Bartolazzi A, Cavaliere R, Bigotti A (1993) Integrin expression in cutaneous malignant melanoma: association of the α3/β1 heterodimer with tumor progression. Int J Cancer 54:68–72
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 1:715–725
Kramer RH, Marks N (1989) Identification of integrin collagen receptors of human melanoma cells. J Biol Chem 264:4684–4688
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 105:1873–1884
Carter WG, Ryan MC, Gahr PF (1991) Epiligrin, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes. Cell 65:599–610
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 52:827–833
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ura, H., Denno, R., Hirata, K. et al. Separate functions of α2β1 and α2β1 integrins in the metastatic process of human gastric carcinomaintegrins in the metastatic process of human gastric carcinoma. Surg Today 28, 1001–1006 (1998). https://doi.org/10.1007/BF02483952
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02483952