Expression of maspin in non-small cell lung cancer and its relationship to vasculogenic mimicry

  • Shiwu Wu (武世伍)
  • Lan Yu (俞 岚)
  • Zenong Cheng (承泽农)
  • Wenqing Song (宋文庆)
  • Lei Zhou (周 蕾)
  • Yisheng Tao (陶仪声)Email author


Maspin belongs to the serine protease inhibitor (serpin) family and has been proven to be a suppressor of tumor growth and metastasis in many types of tumors. The purpose of this study was to investigate the expression of maspin in non-small cell lung cancer (NSCLC) and its relationship to vasculogenic mimicry (VM). A total of 160 specimens of NSCLC were involved in this study and 20 specimens of normal lung tissue served as controls. VM, microvessel density (MVD) and the expression of maspin were detected by using immunohistochemical staining. The results showed that the positive rates of maspin and VM in the NSCLC group were 48.1% (77/160) and 36.9% (59/160), respectively, which were significantly different from those in the control group with the positive rates of maspin and VM being 100% and 0% respectively (P<0.05). VM, MVD and the expression level of maspin were significantly related to tumor differentiation, lymph node metastasis, clinical stages and postoperative survival time (all P<0.05). The maspin expression in patients with squamous cell carcinoma was significantly higher than that in those with adenocarcinoma (P<0.05). The maspin expression was negatively correlated with VM and MVD, and there was a positive correlation between VM and MVD. Maspin-negative expression, VM and high MVD score were negatively related to the 5-year-survival rate. PTNM stages, VM, MVD and maspin expression were independent prognostic factors for NSCLC (P<0.05). It was suggested that the loss of expression of maspin may participate in the invasion and metastasis of NSCLC and it has a positive relationship to VM in NSCLC. Combined detection of maspin, VM and MVD may help predict the progression and prognosis of NSCLC.

Key words

non-small cell lung cancer maspin vasculogenic mimicry microvessel density prognosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jemal A, Center MM, Desantis C, et al. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev, 2010,19(8):1893–1907PubMedCrossRefGoogle Scholar
  2. 2.
    Ramalingam SS, Owonikoko TK, Khuri FR. Lung cancer: new biological insights and recent therapeutic advances. CA Cancer J Clin, 2011,61(2):91–112PubMedCrossRefGoogle Scholar
  3. 3.
    Zou Z, Anisowicz A, Hendrix MJ, et al. Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science, 1994,263(5146):526–529PubMedCrossRefGoogle Scholar
  4. 4.
    Ngamkitidechakul C, Warejcka DJ, Burke JM, et al. Sufficiency of the reactive site loop of maspin for induction of cell-matrix adhesion and inhibition of cell invasion. Conversion of ovalbumin to a maspin-like molecule. J Biol Chem, 2003,278(34):31796–31806PubMedCrossRefGoogle Scholar
  5. 5.
    Odero-Marah VA, Khalkhali-Ellis Z, Chunthapong J, et al. Maspin regulates different signaling pathways for motility and adhesion in aggressive breast cancer cell. Cancer Biol Ther, 2003,2(4):398–403PubMedGoogle Scholar
  6. 6.
    Liu J, Yin S, Reddy N, et al. Bax mediates the apoptosis-sensitizing effect of maspin. Cancer Res, 2004,64(5): 1703–1711PubMedCrossRefGoogle Scholar
  7. 7.
    Zhang W, Shi HY, Zhang M. Maspin overexpression modulates tumor cell apoptosis through the regulation of Bcl-2 family proteins. BMC Cancer, 2005,5:50PubMedCrossRefGoogle Scholar
  8. 8.
    Bailey CM, Khalkhali-Ellis Z, Seftor EA, et al. Biological functions of maspin. J Cell Physiol, 2006,209(3):617–624PubMedCrossRefGoogle Scholar
  9. 9.
    Sheng S. A role of novel serpin maspin in tumor progression: the divergence revealed through efforts to converge. J Cell Physiol, 2006,209(3):631–635PubMedCrossRefGoogle Scholar
  10. 10.
    Khalkhali-Ellis Z. Maspin, the new frontier. Clin Cancer Res, 2006,12(24):7279–7283PubMedCrossRefGoogle Scholar
  11. 11.
    Maniotis AJ, Folberg R, Hess A, et al. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol, 1999,155(3):739–752PubMedCrossRefGoogle Scholar
  12. 12.
    Sood AK, Seftor EA, Fletcher MS, et al. Molecular determinants of ovarian cancer plasticity. Am J Pathol, 2001,158(4):1279–1288PubMedCrossRefGoogle Scholar
  13. 13.
    Heyman L, Leroy-Dudal J, Femands J, et al. Mesothelial vitronectin stimulates migration of ovarian cancer cell. Cell Biol Int, 2010,34(5): 493–502PubMedCrossRefGoogle Scholar
  14. 14.
    Zhao XL, Du J, Zhang SW, et al. A study on vasculogenic mimicry in hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi (Chinese), 2006,14(1):41–44Google Scholar
  15. 15.
    Guzman G, Cotler SJ, Lin AY, et al. A pilot study of vasculogenic mimicry immunohistochemical expression in hepatocellular carcinoma. Arch Pathol Lab Med, 2007, 131(12):1776–1781PubMedGoogle Scholar
  16. 16.
    Liu WB, Xu GL, Ma JL, et al. Osteopontin as a key mediator for vasculogenic mimicry in hepatocellular carcinoma. Tohoku J Exp Med, 2011,224(1):29–39PubMedCrossRefGoogle Scholar
  17. 17.
    Gray DR, Huss WJ, Yau JM, et al. Short-term human prostate primary xenografts: an in vivo model of human prostate cancer vasculature and angiogenesis. Cancer Res, 2004,64(5):1712–1721PubMedCrossRefGoogle Scholar
  18. 18.
    Ahmadi SA, Moinfar M, Gohari Moquaddam K, et al. Practical application of angiogenesis and vasculogenic mimicry in prostatic adenocarcinoma. Arch Iran Med, 2010,13(6):498–503PubMedGoogle Scholar
  19. 19.
    Fan YZ, Sun W, Zhang WZ, et al. Vasculogenic mimicry in human primary gallbladder carcinoma and clinical significance thereof. Zhonghua Yi Xue Za Zhi, 2007,87(3): 145–149PubMedGoogle Scholar
  20. 20.
    Li M, Gu Y, Zhang Z, et al. Vasculogenic mimicry: a new prognostic sign of gastric adenocarcinoma. Pathol Oncol Res, 2010,16(2):259–266PubMedCrossRefGoogle Scholar
  21. 21.
    Vartanian AA, Stepanova EV, Gutorov SL, et al. Prognostic significance of periodic acid-schiff-positive patterns in clear cell renal cell carcinoma. Can J Urol, 2009,16(4):4726–4732PubMedGoogle Scholar
  22. 22.
    Shirakawa K, Wakasugi H, Heike Y, et al. Vasculogenic mimicry and pseudo-comedo formation in breast cancer. Int J Cancer, 2002,99(6):821–828PubMedCrossRefGoogle Scholar
  23. 23.
    Basu GD, Liang WS, Stephan DA, et al. A novel role for cyclooxygenase-2 in regulating vascular channel formation by human breast cancer cell. Breast Cancer Res, 2006,8(6):R69PubMedCrossRefGoogle Scholar
  24. 24.
    Yue WY, Chen ZP. Does vasculogenic mimicry exist in astrocytoma? J Histochem Cytochem, 2005,53(8):997–1002PubMedCrossRefGoogle Scholar
  25. 25.
    Kumada T, Tsuneyama K, Hatta H, et al. Improved 1-h rapid immunostaining method using intermittent microwave irradiation: practicability based on 5 years application in Toyama Medical and Pharmaceutical University Hospital. Mod Pathol, 2004,17(9):1141–1149PubMedCrossRefGoogle Scholar
  26. 26.
    Folberg R, Maniotis AJ. Vasculogenic mimicry. APMIS, 2004,112(7–8):508–525PubMedCrossRefGoogle Scholar
  27. 27.
    Toillon RA, Lagadec C, Page A, et al. Proteomics demonstration that normal breast epithelial cells can induce apoptosis of breast cancers through insulin-like growth factor-binding protein-3 and maspin. Mol Cell Proteomics, 2007,6(7):1239–1247PubMedCrossRefGoogle Scholar
  28. 28.
    Lonardo F, Li X, Kaplun A, et al. The natural tumor suppressor protein maspin and potential application in non-small cell lung cancer. Curr Pharm Des, 2010; 16(16):1877–1881PubMedCrossRefGoogle Scholar
  29. 29.
    Kim S, Han J, Kim J, et al. Maspin expression is transactivated by p63 and is critical for the modulation of lung cancer progression. Cancer Res, 2004,64(19):6900–6905PubMedCrossRefGoogle Scholar
  30. 30.
    Nam E, Park C. Maspin suppresses survival of lung cancer cells through modulation of Akt pathway. Cancer Res Treat, 2010,42(1):42–47PubMedCrossRefGoogle Scholar
  31. 31.
    Takanamil I, Abiko T, Koizumi S, et al. Expression of maspin in non-small-cell lung cancer correlation with clinical features. Clin Lung Cancer, 2008,9(6):361–366CrossRefGoogle Scholar
  32. 32.
    Ni JT, Yi YF, Shi HP. Expression of maspin, p53 and Skp2 in colorectal tumors and their clinicopathological significance. Chin J Cancer Res, 2009,21(2):147–153CrossRefGoogle Scholar
  33. 33.
    Fan YZ, Sun W. Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy. World J Gastrointest Surg, 2010,2(4):117–127PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang S, Guo H, Zhang D, et al. Microcirculation patterns in different stages of melanoma growth. Onclo Rep, 2006,15(1):15–20Google Scholar
  35. 35.
    Forberg R, Hendrix MJ, Maniotis AJ. Vasculogenic mimicry and tumor angiogenesis. Am J Pathol, 2000, 156(2):361–381CrossRefGoogle Scholar
  36. 36.
    Mineo TC, Ambrogi V, Baldi A, et al. Prognostic impact of VEGF, CD31, CD34 and CD105 expression and tumor vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol, 2004,57(6):591–597PubMedCrossRefGoogle Scholar
  37. 37.
    Wang MC, Yang YM, Li XH, et al. Maspin expression and its clinicopathological significance in tumorigenesis and progression of gastric cancer. World J Gastroenterol, 2004,10(5):634–637PubMedGoogle Scholar
  38. 38.
    Sood AK, Fletcher MS, Coffin JE,et al. Functional role of matrix metalloproteinases in ovarian tumor cell plasticity. Am J Obstet Gynecol, 2004,190(4):899–909PubMedCrossRefGoogle Scholar
  39. 39.
    Sun B, Zhang S, Zhao X, et al. Vasculogenic mimicry is associated with poor survival in patients with mesothelial sarcomas and alveolar rhabdomyosarcomas. Int J Oncol, 2004,25(6):1609–1614PubMedGoogle Scholar
  40. 40.
    Wang W, Lin P, Han CH, et al. Vasculogenic mimicry contributes to lymph node metastasis of laryngeal squamous cell carcinoma. J Exp Clin Cancer Res, 2010, 29:60PubMedCrossRefGoogle Scholar
  41. 41.
    Nakashima M, Ohike N, Nagasaki K, et al. Prognostic significance of the maspin tumor suppressor gene in pulmonary adenocarcinoma. J Cancer Res Clin Oncol, 2004,130(8):475–479PubMedCrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Shiwu Wu (武世伍)
    • 1
  • Lan Yu (俞 岚)
    • 1
  • Zenong Cheng (承泽农)
    • 1
  • Wenqing Song (宋文庆)
    • 1
  • Lei Zhou (周 蕾)
    • 1
  • Yisheng Tao (陶仪声)
    • 1
    Email author
  1. 1.Department of Pathology, the First Affiliated Hospital of Bengbu Medical CollegeBengbu Medical CollegeBengbuChina

Personalised recommendations