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. 1992 Jul;90(1):188–195. doi: 10.1172/JCI115835

Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle.

B A Lessey 1, L Damjanovich 1, C Coutifaris 1, A Castelbaum 1, S M Albelda 1, C A Buck 1
PMCID: PMC443080  PMID: 1378853

Abstract

Integrins are a class of cell adhesion molecules that participate in cell-cell and cell-substratum interactions and are present on essentially all human cells. The distribution of nine different alpha and beta integrin subunits in human endometrial tissue at different stages of the menstrual cycle was determined using immunoperoxidase staining. Glandular epithelial cells expressed primarily alpha 2, alpha 3, and alpha 6 (collagen/laminin receptors), while stromal cells expressed predominantly alpha 5 (fibronectin receptor). The presence of alpha 1 on glandular epithelial cells was cycle specific, found only during the secretory phase. Expression of both subunits of the vitronectin receptor, alpha v beta 3, also underwent cycle specific changes on endometrial epithelial cells. Immunostaining for alpha v increased throughout the menstrual cycle, while the beta 3 subunit appeared abruptly on cycle day 20 on luminal as well as glandular epithelial cells. Discordant luteal phase biopsies (greater than or equal to 3 d "out of phase") from infertility patients exhibited delayed epithelial beta 3 immunostaining. These results demonstrate similarities, as well as specific differences, between endometrium and other epithelial tissues. Certain integrin moieties appear to be regulated within the cycling endometrium and disruption of integrin expression may be associated with decreased uterine receptivity and infertility.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M., Buck C. A. Integrins and other cell adhesion molecules. FASEB J. 1990 Aug;4(11):2868–2880. [PubMed] [Google Scholar]
  2. Albelda S. M., Daise M., Levine E. M., Buck C. A. Identification and characterization of cell-substratum adhesion receptors on cultured human endothelial cells. J Clin Invest. 1989 Jun;83(6):1992–2002. doi: 10.1172/JCI114109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albelda S. M. Endothelial and epithelial cell adhesion molecules. Am J Respir Cell Mol Biol. 1991 Mar;4(3):195–203. doi: 10.1165/ajrcmb/4.3.195. [DOI] [PubMed] [Google Scholar]
  4. Albelda S. M., Oliver P. D., Romer L. H., Buck C. A. EndoCAM: a novel endothelial cell-cell adhesion molecule. J Cell Biol. 1990 Apr;110(4):1227–1237. doi: 10.1083/jcb.110.4.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Aplin J. D., Charlton A. K., Ayad S. An immunohistochemical study of human endometrial extracellular matrix during the menstrual cycle and first trimester of pregnancy. Cell Tissue Res. 1988 Jul;253(1):231–240. doi: 10.1007/BF00221758. [DOI] [PubMed] [Google Scholar]
  6. Armant D. R., Kaplan H. A., Mover H., Lennarz W. J. The effect of hexapeptides on attachment and outgrowth of mouse blastocysts cultured in vitro: evidence for the involvement of the cell recognition tripeptide Arg-Gly-Asp. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6751–6755. doi: 10.1073/pnas.83.18.6751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bodary S. C., McLean J. W. The integrin beta 1 subunit associates with the vitronectin receptor alpha v subunit to form a novel vitronectin receptor in a human embryonic kidney cell line. J Biol Chem. 1990 Apr 15;265(11):5938–5941. [PubMed] [Google Scholar]
  8. Buck C. A., Horwitz A. F. Integrin, a transmembrane glycoprotein complex mediating cell-substratum adhesion. J Cell Sci Suppl. 1987;8:231–250. doi: 10.1242/jcs.1987.supplement_8.13. [DOI] [PubMed] [Google Scholar]
  9. Burridge K., Fath K., Kelly T., Nuckolls G., Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988;4:487–525. doi: 10.1146/annurev.cb.04.110188.002415. [DOI] [PubMed] [Google Scholar]
  10. Carter W. G., Kaur P., Gil S. G., Gahr P. J., Wayner E. A. Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes. J Cell Biol. 1990 Dec;111(6 Pt 2):3141–3154. doi: 10.1083/jcb.111.6.3141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carter W. G., Wayner E. A., Bouchard T. S., Kaur P. The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol. 1990 Apr;110(4):1387–1404. doi: 10.1083/jcb.110.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cheresh D. A., Harper J. R. Arg-Gly-Asp recognition by a cell adhesion receptor requires its 130-kDa alpha subunit. J Biol Chem. 1987 Feb 5;262(4):1434–1437. [PubMed] [Google Scholar]
  13. Cheresh D. A., Smith J. W., Cooper H. M., Quaranta V. A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells. Cell. 1989 Apr 7;57(1):59–69. doi: 10.1016/0092-8674(89)90172-4. [DOI] [PubMed] [Google Scholar]
  14. Choy M. Y., Richman P. I., Horton M. A., MacDonald T. T. Expression of the VLA family of integrins in human intestine. J Pathol. 1990 Jan;160(1):35–40. doi: 10.1002/path.1711600109. [DOI] [PubMed] [Google Scholar]
  15. De Luca M., Tamura R. N., Kajiji S., Bondanza S., Rossino P., Cancedda R., Marchisio P. C., Quaranta V. Polarized integrin mediates human keratinocyte adhesion to basal lamina. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6888–6892. doi: 10.1073/pnas.87.17.6888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feinberg R. F., Kliman H. J., Lockwood C. J. Is oncofetal fibronectin a trophoblast glue for human implantation? Am J Pathol. 1991 Mar;138(3):537–543. [PMC free article] [PubMed] [Google Scholar]
  17. Garcia E., Bouchard P., De Brux J., Berdah J., Frydman R., Schaison G., Milgrom E., Perrot-Applanat M. Use of immunocytochemistry of progesterone and estrogen receptors for endometrial dating. J Clin Endocrinol Metab. 1988 Jul;67(1):80–87. doi: 10.1210/jcem-67-1-80. [DOI] [PubMed] [Google Scholar]
  18. Getzenberg R. H., Pienta K. J., Coffey D. S. The tissue matrix: cell dynamics and hormone action. Endocr Rev. 1990 Aug;11(3):399–417. doi: 10.1210/edrv-11-3-399. [DOI] [PubMed] [Google Scholar]
  19. Hayman E. G., Pierschbacher M. D., Ohgren Y., Ruoslahti E. Serum spreading factor (vitronectin) is present at the cell surface and in tissues. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4003–4007. doi: 10.1073/pnas.80.13.4003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Heino J., Ignotz R. A., Hemler M. E., Crouse C., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Concomitant regulation of integrins that share a common beta 1 subunit. J Biol Chem. 1989 Jan 5;264(1):380–388. [PubMed] [Google Scholar]
  21. Hemler M. E., Huang C., Takada Y., Schwarz L., Strominger J. L., Clabby M. L. Characterization of the cell surface heterodimer VLA-4 and related peptides. J Biol Chem. 1987 Aug 25;262(24):11478–11485. [PubMed] [Google Scholar]
  22. Hemler M. E. VLA proteins in the integrin family: structures, functions, and their role on leukocytes. Annu Rev Immunol. 1990;8:365–400. doi: 10.1146/annurev.iy.08.040190.002053. [DOI] [PubMed] [Google Scholar]
  23. Hertle M. D., Adams J. C., Watt F. M. Integrin expression during human epidermal development in vivo and in vitro. Development. 1991 May;112(1):193–206. doi: 10.1242/dev.112.1.193. [DOI] [PubMed] [Google Scholar]
  24. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  25. Ignotz R. A., Heino J., Massagué J. Regulation of cell adhesion receptors by transforming growth factor-beta. Regulation of vitronectin receptor and LFA-1. J Biol Chem. 1989 Jan 5;264(1):389–392. [PubMed] [Google Scholar]
  26. Kao L. C., Caltabiano S., Wu S., Strauss J. F., 3rd, Kliman H. J. The human villous cytotrophoblast: interactions with extracellular matrix proteins, endocrine function, and cytoplasmic differentiation in the absence of syncytium formation. Dev Biol. 1988 Dec;130(2):693–702. doi: 10.1016/0012-1606(88)90361-2. [DOI] [PubMed] [Google Scholar]
  27. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  28. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  29. Lampugnani M. G., Resnati M., Dejana E., Marchisio P. C. The role of integrins in the maintenance of endothelial monolayer integrity. J Cell Biol. 1991 Feb;112(3):479–490. doi: 10.1083/jcb.112.3.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Larjava H., Peltonen J., Akiyama S. K., Yamada S. S., Gralnick H. R., Uitto J., Yamada K. M. Novel function for beta 1 integrins in keratinocyte cell-cell interactions. J Cell Biol. 1990 Mar;110(3):803–815. doi: 10.1083/jcb.110.3.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lessey B. A., Killam A. P., Metzger D. A., Haney A. F., Greene G. L., McCarty K. S., Jr Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle. J Clin Endocrinol Metab. 1988 Aug;67(2):334–340. doi: 10.1210/jcem-67-2-334. [DOI] [PubMed] [Google Scholar]
  32. Lotz M. M., Korzelius C. A., Mercurio A. M. Human colon carcinoma cells use multiple receptors to adhere to laminin: involvement of alpha 6 beta 4 and alpha 2 beta 1 integrins. Cell Regul. 1990 Feb;1(3):249–257. doi: 10.1091/mbc.1.3.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Marchisio P. C., Bondanza S., Cremona O., Cancedda R., De Luca M. Polarized expression of integrin receptors (alpha 6 beta 4, alpha 2 beta 1, alpha 3 beta 1, and alpha v beta 5) and their relationship with the cytoskeleton and basement membrane matrix in cultured human keratinocytes. J Cell Biol. 1991 Feb;112(4):761–773. doi: 10.1083/jcb.112.4.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. McNeely M. J., Soules M. R. The diagnosis of luteal phase deficiency: a critical review. Fertil Steril. 1988 Jul;50(1):1–15. doi: 10.1016/s0015-0282(16)59999-3. [DOI] [PubMed] [Google Scholar]
  35. Navot D., Bergh P. A., Williams M., Garrisi G. J., Guzman I., Sandler B., Fox J., Schreiner-Engel P., Hofmann G. E., Grunfeld L. An insight into early reproductive processes through the in vivo model of ovum donation. J Clin Endocrinol Metab. 1991 Feb;72(2):408–414. doi: 10.1210/jcem-72-2-408. [DOI] [PubMed] [Google Scholar]
  36. Peltonen J., Larjava H., Jaakkola S., Gralnick H., Akiyama S. K., Yamada S. S., Yamada K. M., Uitto J. Localization of integrin receptors for fibronectin, collagen, and laminin in human skin. Variable expression in basal and squamous cell carcinomas. J Clin Invest. 1989 Dec;84(6):1916–1923. doi: 10.1172/JCI114379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ramaswamy H., Hemler M. E. Cloning, primary structure and properties of a novel human integrin beta subunit. EMBO J. 1990 May;9(5):1561–1568. doi: 10.1002/j.1460-2075.1990.tb08275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]
  39. Satyaswaroop P. G., Bressler R. S., de la Pena M. M., Gurpide E. Isolation and culture of human endometrial glands. J Clin Endocrinol Metab. 1979 Apr;48(4):639–641. doi: 10.1210/jcem-48-4-639. [DOI] [PubMed] [Google Scholar]
  40. Sheppard D., Rozzo C., Starr L., Quaranta V., Erle D. J., Pytela R. Complete amino acid sequence of a novel integrin beta subunit (beta 6) identified in epithelial cells using the polymerase chain reaction. J Biol Chem. 1990 Jul 15;265(20):11502–11507. [PubMed] [Google Scholar]
  41. Simon E. E., McDonald J. A. Extracellular matrix receptors in the kidney cortex. Am J Physiol. 1990 Nov;259(5 Pt 2):F783–F792. doi: 10.1152/ajprenal.1990.259.5.F783. [DOI] [PubMed] [Google Scholar]
  42. Sonnenberg A., Janssen H., Hogervorst F., Calafat J., Hilgers J. A complex of platelet glycoproteins Ic and IIa identified by a rat monoclonal antibody. J Biol Chem. 1987 Jul 25;262(21):10376–10383. [PubMed] [Google Scholar]
  43. Sonnenberg A., Linders C. J., Daams J. H., Kennel S. J. The alpha 6 beta 1 (VLA-6) and alpha 6 beta 4 protein complexes: tissue distribution and biochemical properties. J Cell Sci. 1990 Jun;96(Pt 2):207–217. doi: 10.1242/jcs.96.2.207. [DOI] [PubMed] [Google Scholar]
  44. Sonnenberg A., Modderman P. W., Hogervorst F. Laminin receptor on platelets is the integrin VLA-6. Nature. 1988 Dec 1;336(6198):487–489. doi: 10.1038/336487a0. [DOI] [PubMed] [Google Scholar]
  45. Soules M. R., McLachlan R. I., Ek M., Dahl K. D., Cohen N. L., Bremner W. J. Luteal phase deficiency: characterization of reproductive hormones over the menstrual cycle. J Clin Endocrinol Metab. 1989 Oct;69(4):804–812. doi: 10.1210/jcem-69-4-804. [DOI] [PubMed] [Google Scholar]
  46. Tabibzadeh S. Immunoreactivity of human endometrium: correlation with endometrial dating. Fertil Steril. 1990 Oct;54(4):624–631. [PubMed] [Google Scholar]
  47. Zhu B. C., Fisher S. F., Pande H., Calaycay J., Shively J. E., Laine R. A. Human placental (fetal) fibronectin: increased glycosylation and higher protease resistance than plasma fibronectin. Presence of polylactosamine glycopeptides and properties of a 44-kilodalton chymotryptic collagen-binding domain: difference from human plasma fibronectin. J Biol Chem. 1984 Mar 25;259(6):3962–3970. [PubMed] [Google Scholar]

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