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. 1993 May;142(5):1439–1448.

Altered integrin expression in adenocarcinoma of the breast. Analysis by in situ hybridization.

M M Zutter 1, H R Krigman 1, S A Santoro 1
PMCID: PMC1886906  PMID: 8388172

Abstract

The integrin superfamily of adhesion receptors mediates interactions between cells and the extracellular matrix. Our earlier immunohistochemical analysis showed that normal mammary epithelium expressed high levels of the alpha 2 beta 1 collagen/laminin receptor and intermediate levels of the alpha 5 beta 1 fibronectin receptor. In contrast, malignant cells of adenocarcinoma of the breast exhibited marked diminution or loss of the alpha 2 beta 1 and alpha 5 beta 1 integrins. We have now evaluated the level of alpha 2, alpha 5, and beta 1 integrin subunit messenger (m)RNA by in situ hybridization in adenocarcinoma of the breast. Normal breast ducts and ductules expressed high levels of all three integrin subunit mRNAs. Poorly differentiated lesions expressed low to undetectable levels of alpha 2, alpha 5, and beta 1 mRNA. Well- and moderately differentiated lesions expressed all three subunits at intermediate levels. Thus, decreased expression of the alpha 2 beta 1 and alpha 5 beta 1 integrins in mammary carcinoma is the result of decreased steady-state integrin subunit mRNA levels due to altered expression of the integrin genes.

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Selected References

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

  1. Adams J. C., Watt F. M. Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedes alpha 5 beta 1 integrin loss from the cell surface. Cell. 1990 Oct 19;63(2):425–435. doi: 10.1016/0092-8674(90)90175-e. [DOI] [PubMed] [Google Scholar]
  2. Akiyama S. K., Yamada K. M. Biosynthesis and acquisition of biological activity of the fibronectin receptor. J Biol Chem. 1987 Dec 25;262(36):17536–17542. [PubMed] [Google Scholar]
  3. Argraves W. S., Suzuki S., Arai H., Thompson K., Pierschbacher M. D., Ruoslahti E. Amino acid sequence of the human fibronectin receptor. J Cell Biol. 1987 Sep;105(3):1183–1190. doi: 10.1083/jcb.105.3.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brower D. L., Jaffe S. M. Requirement for integrins during Drosophila wing development. Nature. 1989 Nov 16;342(6247):285–287. doi: 10.1038/342285a0. [DOI] [PubMed] [Google Scholar]
  5. Chammas R., Brentani R. Integrins and metastases: an overview. Tumour Biol. 1991;12(6):309–320. doi: 10.1159/000217732. [DOI] [PubMed] [Google Scholar]
  6. Chan B. M., Matsuura N., Takada Y., Zetter B. R., Hemler M. E. In vitro and in vivo consequences of VLA-2 expression on rhabdomyosarcoma cells. Science. 1991 Mar 29;251(5001):1600–1602. doi: 10.1126/science.2011740. [DOI] [PubMed] [Google Scholar]
  7. Chen W. T., Chen J. M., Mueller S. C. Coupled expression and colocalization of 140K cell adhesion molecules, fibronectin, and laminin during morphogenesis and cytodifferentiation of chick lung cells. J Cell Biol. 1986 Sep;103(3):1073–1090. doi: 10.1083/jcb.103.3.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coller B. S., Beer J. H., Scudder L. E., Steinberg M. H. Collagen-platelet interactions: evidence for a direct interaction of collagen with platelet GPIa/IIa and an indirect interaction with platelet GPIIb/IIIa mediated by adhesive proteins. Blood. 1989 Jul;74(1):182–192. [PubMed] [Google Scholar]
  9. Dedhar S. Integrins and tumor invasion. Bioessays. 1990 Dec;12(12):583–590. doi: 10.1002/bies.950121205. [DOI] [PubMed] [Google Scholar]
  10. Dedhar S., Saulnier R. Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes. J Cell Biol. 1990 Feb;110(2):481–489. doi: 10.1083/jcb.110.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Duband J. L., Rocher S., Chen W. T., Yamada K. M., Thiery J. P. Cell adhesion and migration in the early vertebrate embryo: location and possible role of the putative fibronectin receptor complex. J Cell Biol. 1986 Jan;102(1):160–178. doi: 10.1083/jcb.102.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Elices M. J., Hemler M. E. The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9906–9910. doi: 10.1073/pnas.86.24.9906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fearon E. R., Cho K. R., Nigro J. M., Kern S. E., Simons J. W., Ruppert J. M., Hamilton S. R., Preisinger A. C., Thomas G., Kinzler K. W. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science. 1990 Jan 5;247(4938):49–56. doi: 10.1126/science.2294591. [DOI] [PubMed] [Google Scholar]
  14. Fitzgerald L. A., Poncz M., Steiner B., Rall S. C., Jr, Bennett J. S., Phillips D. R. Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor alpha-subunits and platelet glycoprotein IIb. Biochemistry. 1987 Dec 15;26(25):8158–8165. doi: 10.1021/bi00399a021. [DOI] [PubMed] [Google Scholar]
  15. Giancotti F. G., Ruoslahti E. Elevated levels of the alpha 5 beta 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell. 1990 Mar 9;60(5):849–859. doi: 10.1016/0092-8674(90)90098-y. [DOI] [PubMed] [Google Scholar]
  16. Grant D. S., Kleinman H. K., Martin G. R. The role of basement membranes in vascular development. Ann N Y Acad Sci. 1990;588:61–72. doi: 10.1111/j.1749-6632.1990.tb13197.x. [DOI] [PubMed] [Google Scholar]
  17. Hall P. A., Coates P., Lemoine N. R., Horton M. A. Characterization of integrin chains in normal and neoplastic human pancreas. J Pathol. 1991 Sep;165(1):33–41. doi: 10.1002/path.1711650107. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  20. Kirchhofer D., Languino L. R., Ruoslahti E., Pierschbacher M. D. Alpha 2 beta 1 integrins from different cell types show different binding specificities. J Biol Chem. 1990 Jan 15;265(2):615–618. [PubMed] [Google Scholar]
  21. Koretz K., Schlag P., Boumsell L., Möller P. Expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Am J Pathol. 1991 Mar;138(3):741–750. [PMC free article] [PubMed] [Google Scholar]
  22. Koukoulis G. K., Virtanen I., Korhonen M., Laitinen L., Quaranta V., Gould V. E. Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Correlations with their functions as receptors and cell adhesion molecules. Am J Pathol. 1991 Oct;139(4):787–799. [PMC free article] [PubMed] [Google Scholar]
  23. Languino L. R., Gehlsen K. R., Wayner E., Carter W. G., Engvall E., Ruoslahti E. Endothelial cells use alpha 2 beta 1 integrin as a laminin receptor. J Cell Biol. 1989 Nov;109(5):2455–2462. doi: 10.1083/jcb.109.5.2455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Liotta L. A., Rao C. N., Barsky S. H. Tumor invasion and the extracellular matrix. Lab Invest. 1983 Dec;49(6):636–649. [PubMed] [Google Scholar]
  25. Liotta L. A., Stetler-Stevenson W. G., Steeg P. S. Cancer invasion and metastasis: positive and negative regulatory elements. Cancer Invest. 1991;9(5):543–551. doi: 10.3109/07357909109018952. [DOI] [PubMed] [Google Scholar]
  26. Pignatelli M., Hanby A. M., Stamp G. W. Low expression of beta 1, alpha 2 and alpha 3 subunits of VLA integrins in malignant mammary tumours. J Pathol. 1991 Sep;165(1):25–32. doi: 10.1002/path.1711650106. [DOI] [PubMed] [Google Scholar]
  27. Pignatelli M., Smith M. E., Bodmer W. F. Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas. Br J Cancer. 1990 Apr;61(4):636–638. doi: 10.1038/bjc.1990.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Plantefaber L. C., Hynes R. O. Changes in integrin receptors on oncogenically transformed cells. Cell. 1989 Jan 27;56(2):281–290. doi: 10.1016/0092-8674(89)90902-1. [DOI] [PubMed] [Google Scholar]
  29. Poste G., Fidler I. J. The pathogenesis of cancer metastasis. Nature. 1980 Jan 10;283(5743):139–146. doi: 10.1038/283139a0. [DOI] [PubMed] [Google Scholar]
  30. Prosser I. W., Stenmark K. R., Suthar M., Crouch E. C., Mecham R. P., Parks W. C. Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. Am J Pathol. 1989 Dec;135(6):1073–1088. [PMC free article] [PubMed] [Google Scholar]
  31. Reichardt L. F., Tomaselli K. J. Extracellular matrix molecules and their receptors: functions in neural development. Annu Rev Neurosci. 1991;14:531–570. doi: 10.1146/annurev.ne.14.030191.002531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sanes J. R. Extracellular matrix molecules that influence neural development. Annu Rev Neurosci. 1989;12:491–516. doi: 10.1146/annurev.ne.12.030189.002423. [DOI] [PubMed] [Google Scholar]
  34. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Santoro S. A., Rajpara S. M., Staatz W. D., Woods V. L., Jr Isolation and characterization of a platelet surface collagen binding complex related to VLA-2. Biochem Biophys Res Commun. 1988 May 31;153(1):217–223. doi: 10.1016/s0006-291x(88)81211-7. [DOI] [PubMed] [Google Scholar]
  36. Staatz W. D., Rajpara S. M., Wayner E. A., Carter W. G., Santoro S. A. The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg++-dependent adhesion of platelets to collagen. J Cell Biol. 1989 May;108(5):1917–1924. doi: 10.1083/jcb.108.5.1917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Streuli C. H., Bailey N., Bissell M. J. Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity. J Cell Biol. 1991 Dec;115(5):1383–1395. doi: 10.1083/jcb.115.5.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Takada Y., Hemler M. E. The primary structure of the VLA-2/collagen receptor alpha 2 subunit (platelet GPIa): homology to other integrins and the presence of a possible collagen-binding domain. J Cell Biol. 1989 Jul;109(1):397–407. doi: 10.1083/jcb.109.1.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Volk T., Fessler L. I., Fessler J. H. A role for integrin in the formation of sarcomeric cytoarchitecture. Cell. 1990 Nov 2;63(3):525–536. doi: 10.1016/0092-8674(90)90449-o. [DOI] [PubMed] [Google Scholar]
  40. Zutter M. M., Fong A. M., Krigman H. R., Santoro S. A. Differential regulation of the alpha 2 beta 1 and alpha IIb beta 3 integrin genes during megakaryocytic differentiation of pluripotential K562 cells. J Biol Chem. 1992 Oct 5;267(28):20233–20238. [PubMed] [Google Scholar]
  41. Zutter M. M., Mazoujian G., Santoro S. A. Decreased expression of integrin adhesive protein receptors in adenocarcinoma of the breast. Am J Pathol. 1990 Oct;137(4):863–870. [PMC free article] [PubMed] [Google Scholar]
  42. Zutter M. M., Santoro S. A. Widespread histologic distribution of the alpha 2 beta 1 integrin cell-surface collagen receptor. Am J Pathol. 1990 Jul;137(1):113–120. [PMC free article] [PubMed] [Google Scholar]

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