Skip to main content
SpringerLink
Log in

Integrin expression in non-small cell carcinoma of the lung

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Summary

Alteration of integrin expression in a number of different malignant diseases has been recognized, with a trend of downregulation of collagen-laminin binding integrin expression in epithelial tumor types noted. This study evaluated the expression of a panel of integrin subunits that included subunits that form receptors that bind to collagen and laminin (α2, α3, α6 β4) and subunits that form receptors that bind to fibronectin and fibrinogen (α5, αv, β3, β6) in 51 specimens of non-small cell carcinoma (NSCCA) of the lung by use of immunohistochemistry. Integrin expression was then correlated with histologic type (squamous vs. adenocarcinoma), absence or presence of hilar or mediastinal nodal metastasis at resection, and cellular differentiation (well or poorly differentiated). In general, downregulation of the collagen-laminin binding subunits was noted in tumor cells of the NSCCA specimens when compared to the progenitor normal bronchial epithelium. No differences were noted in integrin expression between squamous cell and adenocarcinoma or between node-positive or node-negative tumors. However, downregulation of the integrin subunit α3 was noted to be significantly more common in poorly differentiated tumors (p = 0.02) and several of the other collagen-laminin binding subunits also appeared to be more downregulated in poorly differentiated tumors. No upregulation was seen in the α5 subunit of the fibronectin receptor or the β3 subunit of the vitronectin receptor, however, approximately 50% of tumors showed upregulation of the β6 subunit, the great majority of these being well-differentiated, node-negative tumors. Downregulation of the collagen-laminin integrins may thus be associated with differentiation of NSCCA, but not metastasis, and may serve as an adjunctive prognostic marker of disease. The β6 subunit appears to be associated with malignant transformation, but may serve as a positive prognostic factor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wingo PA, Tong T, Bolden S: Cancer statistics, 1995. CA 45: 8–30, 1995

    Google Scholar 

  2. Travis WD, Travis LB, Devesa SS: Lung cancer. Cancer 75: 191–202, 1995

    Google Scholar 

  3. Fidler IJ: Origin and biology of cancer metastasis. Cytometry 10: 673–680, 1989

    Google Scholar 

  4. Juliano RL: Membrane receptors for extracellular matrix macromolecules: relationship to cell adhesion and tumor metastasis. Biochim Biophys Acta 948: 261–278, 1987

    Google Scholar 

  5. Albelda SM: Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest 68: 4–17, 1993

    Google Scholar 

  6. Albelda SM: Endothelial and epithelial cell adhesion molecules. Am J Resp Cell Mol Biol 4: 195–203, 1991

    Google Scholar 

  7. Albelda SM, Daise M, Levine EN, Buck CA: Identification and characterization of cell-substratum adhesion receptors on cultured human adult large vessel endothelial cells. J Clin Invest 83: 1992–2002, 1989

    Google Scholar 

  8. Albelda SM, Mette SA, Elder DE, Stewart RM, Damjanovich L, Herlyn M, Buck CA: Integrin distribution in malignant melanomas: Association of the β3 subunit with tumor progression. Cancer Res 50: 6757–6764, 1990

    Google Scholar 

  9. Felding-Habermann B, Mueller BM, Romerdahl CA, Cheresh DA: Involvement of integrin αV gene expression in human melanoma tumorigencity. J Clin Invest 89: 2018–2022, 1992

    Google Scholar 

  10. Pignatelli M, Hanby AM, Stamp GWH: Low expression of β1, α2 and α3 subunits of VLA integrins in malignant mammary tumors. J Pathol 165: 25–32, 1991

    Google Scholar 

  11. Jones JL, Critchley DR, Walker RA: Alteration in stromal protein and integrin expression in breast - a marker of premalignant change? J Path 167: 399–406, 1992

    Google Scholar 

  12. Natali PG, Nicotra MR, Botti C, Mottolese M, Bigotti A, Segatto O: Changes in expression of α6/β4 integrin heterodimers in primary and metastatic breast cancer. Br J Cancer 66: 318–322, 1992

    Google Scholar 

  13. Bonkhoff H, Stein U, Remberger K: Differential expression of α6 and α2 very late antigen integrins in the normal, hyperplastic and neoplastic prostate: simultaneous demonstration of cell surface receptors and their extracellular ligands. Hum Pathol 24: 243–248, 1993

    Google Scholar 

  14. Weinel RJ, Rosendahl A, Neumann K, Chaloupka B, Erp D, Rothmund M, Santoso S: Expression and function of VLA-α3, -α5, and -α6 integrin receptors in pancreatic carcinoma. Int J Cancer 52: 827–833, 1992

    Google Scholar 

  15. Korhonen M, Laitinen L, Ylanne J, Koukoulis GK, Quaranta V, Juusela H, Gould VE, Virtanen I: Integrin distribution in renal cell carcinomas of various grades of malignancy. Am J Pathol 141: 1161–1171, 1992

    Google Scholar 

  16. Nigam AK, Savage FJ, Boulos PB, Stamp GWH, Liu D, Pignatelli M: Loss of cell-cell and cell-matrix adhesion molecules in colorectal cancer. Br J Cancer 68: 507–514, 1993

    Google Scholar 

  17. Pignatelli M: Integrin cell adhesion molecules and colorectal cancer. J Pathol 162: 95–97, 1990

    Google Scholar 

  18. Liebert M, Washington R, Stein J, Wedemeyer G, Grossman HB: Expression of the VLA-β1 integrin family in bladder cancer. Am J Pathol 144: 1016–1022, 1993

    Google Scholar 

  19. Damjanovich L, Albelda SM, Mette SA, Buck CA: Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. Am J Respir Cell Mol Biol 6: 197–206, 1992

    Google Scholar 

  20. Costantini RM, Falconi R, Battista P, Zupi G, Kennel SJ, Colasante A, Venturo I, Curcio CG, Sacchi A: Integrin (α6/β4) expression in human lung cancer as monitored by specific monoclonal antibodies. Cancer Res 50: 6107–6112, 1990

    Google Scholar 

  21. Miettinen M, Castello R, Wayner E, Schwarting R: Distribution of VLA integrins in solid tumors: emergence of tumor-type-related expression patterns in carcinomas and sarcomas. Am J Pathol 142: 1009–1018, 1993

    Google Scholar 

  22. Roussel E, Gingras M-C, Ro JY, Branch C, Roth JA: Loss of α1β1 and reduced expression of other β1 integrins and CAM in lung adenocarcinoma compared with pneumocytes. J Surg Oncol 56: 198–208, 1994

    Google Scholar 

  23. Sonnenberg A, Modderman PW, Hogervorst F: Laminin receptor on platelets is the integrin VLA-6. Nature 336: 487–489, 1988

    Google Scholar 

  24. Cheresh D, Harper J: ARG-GLY-ASP recognition by a cell adhesion receptor requires its 130 kDa subunit. J Biol Chem 262: 17703–17711, 1987

    Google Scholar 

  25. Brass LF, Shattil SJ, Kunicki TJ, Bennett JS: Effect of calcium on the stability of the platelet membrane glyprotein IIb/IIIa complex. J Biol Chem 260: 7875–7881, 1985

    Google Scholar 

  26. Kennel SJ, Godfrey V, Ch'ang LY, Lankford TK, Foote LJ, Makkinje A: The β4 subunit of the integrin family is displayed on a restricted subset of endothelium in mice. J Cell Sci 101: 145–150, 1992

    Google Scholar 

  27. Weinacker A, Chen A, Agrez M, Cone RI, Nishimura S, Wayner E, Pytela R, Sheppard D: Role of the integrin αVβ6 in cell attachment to fibronectin. J Biol Chem 269: 6940–6948, 1994

    Google Scholar 

  28. Mette SA, Pilewski J, Buck CA, Albelda SM: The distribution of integrin cell adhesion receptors on normal bronchial epithelial cells and lung cancer cellsin vitro andin vivo. Am J Respir Cell Mol Biol 8: 562–572, 1993

    Google Scholar 

  29. Pignatelli M, Cardillo MR, Hanby A, Stamp G: Integrins and their accessory adhesion molecules in mammary carcinomas: Loss of polarization in poorly differentiated tumors. Hum Pathol 23: 1159–1166, 1992

    Google Scholar 

  30. Bottini C, Miotti S, Fiorucci S, Facheris P, Menard S, Colnaghi MI: Polarization of the α6β4 integrin in ovarian carcinoma. Int J Cancer 54: 261–267, 1993

    Google Scholar 

  31. Juhasz I, Murphy GF, Herlyn M, Albelda SM: Regulation of extracellular matrix proteins and integrin cell substratum receptors on epithelium during cutaneous wound healingin vivo. Am J Pathol 143: 1458–1469, 1993

    Google Scholar 

  32. Hertle MD, Kubler D, Leigh IM, Watt FM: Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. J Clin Invest 89: 1892–1901, 1992

    Google Scholar 

  33. Pignatelli M, Smith MEF, Bodmer WF: Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas. Br J Cancer 61: 636–638, 1991

    Google Scholar 

  34. Chen FA, Reoasky EA, Bankert RB: Human lung tumorassociated antigen identified as an extracellular matrix adhesion molecule. J Exp Med 173: 1111–1119, 1991

    Google Scholar 

  35. Gui GPH, Wells CA, Browne PD, Yeomans P, Jordan S, Puddefoot JR, Vinson GP, Carpenter R: Integrin expression in primary breast cancer and its relation to axillary node status. Surgery 117: 102–108, 1995

    Google Scholar 

  36. Leak LV, Jamuar: Ultrastructure of pulmonary lymphatic vessels. Am Rev Respir Dis 128: S59-S65, 1983

    Google Scholar 

  37. Breuss JM, Gallo J, DeLisser HM, Klimanskaya IV, Folkesson HG, Pittet JF, Nishimura SL, Aldape K, Landers DV, Carpenter W, Gillet N, Sheppard D, Matthay MA, Albelda SM, Kramer RH, Pytela R: Expression of the β6 integrin in development, inflammation, wound healing, and neoplasia suggests a role in epithelial remodeling. J Cell Sci, in press

  38. Agrez M, Chen A, Cone RI, Pytela R, Sheppard D: The alpha-v beta-6 integrin promotes proliferation of colon carcinoma cells through a unique region of the beta 6 cytoplasmic domain. J Cell Biol 127: 547–556, 1994

    Google Scholar 

  39. Koretz K, Schlag P, Boumsell L, Muller P: Expression of VLA-α2, VLA-α6, and VLA-β1 in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Am J Pathol 138: 741–750, 1991

    Google Scholar 

  40. Freidrichs K, Ruiz P, Franke F, Gille I, Terpe H-J, Imhof BA: High expression level of α6 integrin in human breast carcinoma is correlated with reduced survival. Cancer Res 55: 901–906, 1995

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Thoracic Surgery Section, Department of Surgery, University of Pennsylvania Medical Center, 19104, Philadelphia, PA, USA

    W. Roy Smythe, Joseph E. Bavaria & Larry R. Kaiser

  2. Pulmonary/Crital Care Division, Department of Medicine, The Thoracic Oncology Research Laboratory: University of Pennsylvania Medical Center, 19104, Philadelphia, PA, USA

    Elizabeth LeBel & Steven M. Albelda

Authors
  1. W. Roy Smythe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth LeBel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph E. Bavaria
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Larry R. Kaiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steven M. Albelda
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smythe, W.R., LeBel, E., Bavaria, J.E. et al. Integrin expression in non-small cell carcinoma of the lung. Cancer Metast Rev 14, 229–239 (1995). https://doi.org/10.1007/BF00690294

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00690294

Key words

Search

Navigation