Abstract
Alpha 6 integrin is an adhesion molecule that connects cells with extracellular matrix molecules of the laminin family. The laminin interaction seems to be essential for cell differentiation during embryogenesis and for the subsequent maintenance of tissue integrity in the adult. Alpha 6 integrin can also interact with laminin-independent cellular ligands and in this way plays a role in homing of leucocytes. Furthermore, in cancer biology α6 integrin has an important role in metastasis and as a possible new prognostic factor; exact knowledge of α6 integrin distribution in normal human tissues is therefore a crucial element. By immuno-histochemical methods we have screened α6 integrin expression of representative human tissues from the adult and the embryonic organism. All tested epithelia were α6 integrin positive, except for the endocrine cells of the pancreas and the adrenal glands. Heterogeneous staining was found on non-epithelial tissues. Strong staining was evident in peripheral nerves (Schwann cells), germ and Sertoli cells, endothelia, and smooth muscle cells of the myometrium. Weak staining was found in nerve cells of the stratum granulosum, the microglia, Kupffer's cells and stromal cells of the ovary. All fibroblasts, striated muscle cells and astrocytes were negative. The tissue distribution of α6 integrin and the semi-quantitative estimation of their expression level should provide a better understanding of α6 integrin function under normal and phathological conditions, in particular in tumour progression.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albelda SM, Buck CA (1990) Integrins and other cell adhesion molecules. FASEB J 4:2868–2880
Baier H, Bonhoeffer F (1991) Axon guidance of gradients of a target-derived component. Science 255:472–475
Blood CH, Zetter BR (1993) Laminin regulates a tumor cell chemotaxis receptor through the laminin-binding integrin subunit alpha 6. Cancer Res 53:2661–2666
Bloom W, Fawcett DW (1975) Histology. WB Saunders Company, Philadelphia, pp 1033
Burdsal CA, Damsky CH, Pedersen RA (1993) The role of E-cadherin and integrins in mesoderm differentiation and migration at the mammalian primitive streak. Development 118:829–844
Cooper HM, Tamura RN, Quaranta V (1991) The major laminin receptor of mouse embryonic stem cells is a novel isoform of the alpha 6 beta 1 integrin. J Cell Biol 115:843–850
Cordell JL, Falini B, Erber WN, Gosh AK, Abdulaziz Z, Macdonald S, Pulford KAF, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229
DeLuca M, Tamura RN, Kajiji S, Bondanza S, Cancedda R, Rossino P, Marchisio PC, Quaranta V (1990) Polarized integrin alpha 6 beta 4 mediates keratinocytes adhesion to basal lamina. Proc Natl Acad Sci USA 87:6888–6892
Hierck BP, Thorsteinsdóttir S, Niessen CM, Freund E, Iperen LV, Feyen A, Hogervorst F, Poelmann RE, Mummery CL, Sonnenberg A (1993) Variants of the α6β 1 laminin receptor in early murine development: distribution, molecular cloning and chromosomal localization of the mouse integrin α6 subunit. Cell Adhesion Commun 1:33–53
Hogervorst F (1993) Biochemical characterization and tissue distribution of the A and B variants of the integrin alpha 6 subunit. J Cell Biol 121:179–191
Hogervorst F, Kuikman I, van Kessel A, Sonnenberg A (1991) Molecular cloning of the human alpha 6 integrin subunit. Alternative splicing of alpha 6 mRNA and chromosomal localization of the alpha 6 and beta 4 genes. Eur J Biochem 199:425–433
Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25
Imhof BA, Ruiz P, Hesse B, Palacios R, Dunon D (1991) EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus. J Cell Biol 114:1069–1078
Kennel SJ, Godfrey V, Chang LY, Lankford TK, Foote LJ, Makkinje A (1992) The beta 4 subunit of the integrin family is displayed on a restricted subset of endothelium in mice. J Cell Sci 101:145–150
Lee EC, Lotz MM, Steele GJ, Mercurio AM (1992) The integrin alpha 6 beta 4 is a laminin receptor. J Cell Biol 117:671–678
Lenter M, Uhlig H, Hamann A, Jenö P, Imhof BA, Vestweber D (1993) A monoclonal antibody against an activation epitope on mouse integrin chain β1 blocks adhesion of lymphocytes to the endothelial integrin α6β1. Proc Natl Acad Sci USA 90:51–55
Lin C-S, Zhang K, Kramer R (1993) Alpha 6 integrin is up-regulated in step increments accompanying neoplastic transformation and tumorigenic conversion of human fibroblasts. Cancer Res 53:2950–2953
Quaranta V (1990) Epithelial integrins. Cell Differ Dev 32:361–366
Ruiz P, Dunon D, Sonnenberg A, Imhof BA (1993) Suppression of mouse melanoma metastasis by EA-1, a monoclonal antibody specific for alpha 6 integrins. Cell Adhesion Commun 1:67–81
Shaw LM, Messier JM, Mercurio AM (1990) The activation dependent adhesion of macrophages to laminin involves cytoskeletal anchoring and phosphorylation of the alpha 6 beta 1 integrin. J Cell Biol 110:2167–2174
Song WK, Weiwang W, Foster RF, Bielser DA, Kaufman SJ (1992) H36-alpha 7 is a novel integrin alpha chain that is developmentally regulated during skeletal myogenesis. J Cell Biol 117:643–657
Sonnenberg A, Linders CJT (1990) The alpha 6 beta 1 (VLA-6) and alpha 6 beta 4 protein complexes: tissue distribution and biochemical properties. J Cell Sci 96:207–217
Sonnenberg A, Modderman PW, Hogervorst F (1988) Laminin receptor on platelets in the integrin VLA-6. Nature 336:487–489
Sonnenberg A, Linders CJ, Modderman PW, Damsky CH, Aumailley M, Timpl R (1990) Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8. J Cell Biol 110:2145–2155
Sorokin L, Sonnenberg A, Aumailley M, Timpl R, Ekblom P (1990) Recognition of the laminin E8 cell-binding site by an integrin possessing the alpha 6 subunit is essential for epithelial polarization in developing kidney tubules. J Cell Biol 111:1265–1273
Tryggvason K (1993) The laminin family. Curr Opin Cell Biol 5:877–882
Wolf GT, Carey TE, Schmaltz SP, McClathey KD, Poore J, Glaser L, Hayashida SJS, Hsu S (1990) Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck. J Natl Cancer Inst 82:1566–1572
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Terpe, H.J., Stark, H., Ruiz, P. et al. Alpha 6 integrin distribution in human embryonic and adult tissues. Histochemistry 101, 41–49 (1994). https://doi.org/10.1007/BF00315830
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00315830