Skip to main content
SpringerLink
Log in

Different Biomarkers in Non-Small Cell Lung Cancer in Blood Vessel Invasion

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

In clinical settings, lung cancer is divided into small cell lung cancer and non-small cell lung cancer, and chemotherapy is depended on the difference. Using the same chemotherapy treatment, different effects and prognosis can be seen among squamous-cell carcinoma and adenocarcinoma. These differences indicate that there may be various methods of invasion and immunity between squamous-cell carcinoma and adenocarcinoma. Blood vessel invasion and tumor immune escape play very important roles in the progression and metastasis of cancer, and CD105 and integrins are novel therapeutic targets. We assessed the possible association of CD105 expression and integrins with TNM classification in patients with two types of NSCLC. A total of 72 patients with resected Non-Small Cell Lung Cancer (NSCLC) were reviewed retrospectively. Integrin β1, β2, β3, and α5β1 are assayed by immunofluorescence and integrin α5β1 using immunoblot. Intratumoral microvessel density was determined with an anti-CD34 mAb and an anti-CD105 mAb. Invasive ability was assayed with MMP2 and MMP9 using immunofluorescence. The expressions of all integrins, CD105, and CD34 are low in the normal lung tissue and highly expressed in the cancer niche compared to the adjacent tissues. CD105 is highly expressed in the adenocarcinoma niche compared to the squamous-cell carcinoma in NSCLC. The expressions of both MMP2 and MMP9 are low in the normal lung tissue and highly expressed in adjacent tissues. This study shows that blood vessel invasion appears to be an independent negative prognosticator in surgically managed types of NSCLC. However, adequately designed large prospective studies are warranted to confirm the present findings.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., et al. (2011). Global cancer statistics. CA Cancer Journal for Clinicians, 61, 69–90.

    Article  Google Scholar 

  2. Wang, J., Chen, J., Chen, X., Wang, B., Li, K., & Bi, J. (2011). Blood vessel invasion as a strong independent prognostic indicator in non-small cell lung cancer: A systematic review and meta-analysis. PLoS One, 6, e28844.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Leon, S. P., Folkerth, R. D., & Black, P. M. (1996). Microvessel density is a prognostic indicator for patients with astroglial brain tumors. Cancer, 77, 362–372.

    Article  PubMed  CAS  Google Scholar 

  4. Reinmuth, N., Piegelbrock, E., Raedel, M., et al. (2007). Prognostic significance of vessel architecture and vascular stability in non-small cell lung cancer. Lung Cancer, 55, 53–60.

    Article  PubMed  Google Scholar 

  5. Birlik, B., Canda, S., & Ozer, E. (2006). Tumor vascularity is of prognostic significance in adult, but not paediatric astrocytomas. Neuropathology and Applied Neurobiology, 32, 532–538.

    Article  PubMed  CAS  Google Scholar 

  6. Elliott, R. L., & Blobe, G. C. (2005). Role of transforming growth factor beta in human cancer. Journal of Clinical Oncology, 23, 2078–2093.

    Article  PubMed  CAS  Google Scholar 

  7. Yamamoto, T., Kozawa, O., Tanabe, K., et al. (2001). Involvement of p38 MAP kinase in TGF-beta-stimulated VEGF synthesis in aortic smooth muscle cells. Journal of Cellular Biochemistry, 82, 591–598.

    Article  PubMed  CAS  Google Scholar 

  8. Tanaka, F., Otake, Y., Yanagihara, K., et al. (2001). Evaluation of angio-genesis in non-small cell lung cancer: Comparison between anti-CD34 antibody and anti-CD105 antibody. Clinical Cancer Research, 7, 3410–3415.

    PubMed  CAS  Google Scholar 

  9. Fonsatti, E., Nicolay, H. J., Altomonte, M., Covre, A., & Maio, M. (2009). Targeting cancer vasculature via endoglin/CD105: a novel antibody-based diagnostic and therapeutic strategy in solid tumors. Cardiovascular Research, 86, 12–19.

    Article  PubMed  Google Scholar 

  10. Avraamides, C. J., Garmy-Susini, B., & Varner, J. A. (2008). Integrins in angiogenesis and lymphangiogenesis. Nature Reviews Cancer, 8, 604–617.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Giancotti, F. G., & Tarone, G. (2003). Positional control of cell fate through joint integrin/receptor protein kinase signaling. Annual Review of Cell and Developmental Biology, 19, 173–206.

    Article  PubMed  CAS  Google Scholar 

  12. Mizejewski, G. J. (1999). Role of integrins in cancer: survey of expression patterns. Proceedings of the Society for Experimental Biology and Medicine, 222, 124–138.

    Article  PubMed  CAS  Google Scholar 

  13. Hwang, R., & Varner, J. (2004). The role of integrins in tumor angiogenesis. Hematology/oncology Clinics of North America, 18, 991–1006.

    Article  PubMed  Google Scholar 

  14. Goldstraw, P. (2009). International association for the study of lung cancer. Staging manual in thoracic oncology. Orange Park, FL: Editorial Rx Press.

    Google Scholar 

  15. Liu, Y., Huo, X., Pang, X. P., Zong, X. H., Meng, X., & Liu, G. L. (2008). Musclin inhibits insulin activation of Akt/protein kinase B in rat skeletal muscle. Journal of International Medical Research, 36, 496–504.

    Article  PubMed  CAS  Google Scholar 

  16. Dingemans, A. M., Van den Boogaard, V., Vosse, B. A., Van Suylen, R. J., Griffioen, A. W., & Thijssen, V. L. (2010). Integrin expression profiling identifies integrin alpha5 and beta1 as prognostic factors in early stage non-small cell lung cancer. Molecular Cancer, 9, 152.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Adachi, M., Taki, T., Higashiyama, M., Kohno, N., Inufusa, H., & Miyake, M. (2000). Significance of integrin alpha5 gene expression as a prognostic factor in node-negative non-small cell lung cancer. Clinical Cancer Research, 6, 96–101.

    PubMed  CAS  Google Scholar 

  18. Han, J. Y., Kim, H. S., Lee, S. H., Park, W. S., Lee, J. Y., & Yoo, N. J. (2003). Immunohistochemical expression of integrins and extracellular matrix proteins in non-small cell lung cancer: correlation with lymph node metastasis. Lung Cancer, 41, 65–70.

    Article  PubMed  Google Scholar 

  19. Okamura, M., Yamaji, S., Nagashima, Y., Nishikawa, M., Yoshimoto, N., Kido, Y., et al. (2004). Prognostic value of integrin beta1-ILKpAkt signaling pathway in non-small cell lung cancer. Human Pathology, 38, 1081–1091.

    Article  Google Scholar 

  20. Mott, J. D., & Werb, Z. (2004). Regulation of matrix biology by matrix metalloproteinases. Current Opinion in Cell Biology, 16, 558–564.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Shapiro, S. D. (2003). Proteolysis in the lung. European Respiratory Journal, 44, 30s–32s.

    Article  PubMed  CAS  Google Scholar 

  22. Galis, Z. S., & Khatri, J. J. (2002). Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circulation Research, 90, 251–262.

    PubMed  CAS  Google Scholar 

  23. Pepper, M. S. (2001). Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 1104–1117.

    Article  PubMed  CAS  Google Scholar 

  24. Vaisar, T., Kassim, S. Y., Gomez, I. G., Green, P. S., Hargarten, S., Gough, P. J., et al. (2009). MMP-9 sheds the beta2 integrin subunit (CD18) from macrophages. Molecular and Cellular Proteomics, 8, 1044–1060.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Becker, P. S., Nilsson, S. K., Li, Z., Berrios, V. M., Dooner, M. S., Cooper, C. L., et al. (1999). Adhesion receptor expression by hematopoietic cell lines and murine progenitors: modulation by cytokines and cell cycle status. Experimental Hematology, 27, 533–541.

    Article  PubMed  CAS  Google Scholar 

  26. Orschell-Traycoff, C. M., Hiatt, K., Dagher, R. N., Rice, S., Yoder, M. C., & Srour, E. F. (2000). Homing and engraftment potential of Sca-1(+)lin(-) cells fractionated on the basis of adhesion molecule expression and position in cell cycle. Blood, 96, 1380–1387.

    PubMed  CAS  Google Scholar 

  27. Chavakis, E., Aicher, A., Heeschen, C., Sasaki, K., Kaiser, R., El Makhfi, N., et al. (2005). Role ofβ2-integrins for homing and neovascularization capacity of endothelial progenitor cells. Journal of Experimental Medicine, 201, 63–72.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Damjanovich, L., Albelda, S. M., Mette, S. A., & Buck, C. A. (1992). Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. American Journal of Respiratory Cell and Molecular Biology, 6, 197–206.

    Article  PubMed  CAS  Google Scholar 

  29. Smith, S. J., Tilly, H., Ward, J. H., Macarthur, D. C., Lowe, J., Coyle, B., et al. (2012). CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma. Acta Neuropathologica, 124, 99–110.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rau, K. M., Huang, C. C., Chiu, T. J., Chen, Y. Y., Lu, C. C., Liu, C. T., et al. (2012). Neovascularization evaluated by CD105 correlates well with prognostic factors in breast cancers. Experimental and Therapeutic medicine, 4, 231–236.

    PubMed  PubMed Central  Google Scholar 

  31. Chamberlain, G., Fox, J., Ashton, B., & Middleton, J. (2007). Concise review: Mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells, 25, 2739–2749.

    Article  PubMed  CAS  Google Scholar 

  32. Zijlmans, H. J., Fleuren, G. J., Hazelbag, S., et al. (2009). Expression of endoglin (CD105) in cervical cancer. British Journal of Cancer, 100, 1617–1626.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  33. Hoffman, P. C., Mauer, A. M., & Vokes, E. E. (2000). Lung cancer. Lancet, 355, 479–485.

    Article  PubMed  CAS  Google Scholar 

  34. Hart, I. R., & Saini, A. (1992). Biology of tumor metastasis. Lancet, 339, 1453–1457.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, 18 Ziqiang Street, Changchun, Jilin, China

    Chunyu Zhang & Jie Zhang

  2. Department of Respiratory Medicine, Siping Central Hospital, No. 89, Nanyingbin Road, Tiexi District, Siping, 136000, Jilin, China

    Chunyu Zhang

  3. Department of Stem Cell Clinical Application Central, Siping Central Hospital, No. 89, Nanyingbin Road, Tiexi District, Siping, 136000, Jilin, China

    Ying Liu & Shengnan Guo

Authors
  1. Chunyu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shengnan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jie Zhang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, C., Liu, Y., Guo, S. et al. Different Biomarkers in Non-Small Cell Lung Cancer in Blood Vessel Invasion. Cell Biochem Biophys 70, 777–784 (2014). https://doi.org/10.1007/s12013-014-9981-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-9981-9

Keywords

Search

Navigation