Increased expression of CD147 and MMP-9 is correlated with poor prognosis of salivary duct carcinoma

  • Songlin Piao
  • Shu Zhao
  • Fulin Guo
  • Jie Xue
  • Guodong Yao
  • Zhili Wei
  • Qi Huang
  • Yao Sun
  • Bin ZhangEmail author
Original Paper



The aim of this study was to investigate expression of CD147 and MMP-9 in salivary duct carcinoma (SDC) so as to determine whether these two genes may be correlated with poor prognosis of SDC.


We examined the significance of the CD147 and MMP-9 expression in SDC (n = 35), non-cancerous salivary tissue (n = 20) in previously untreated patients using immunohistochemical staining. Furthermore, we analyzed the correlation between the expression of these two genes and various clinicopathologic factors including survival status of patients with SDC.


Positive stain of CD147 and MMP-9 was seen in all 35 cases of tumor samples. A statistical correlation was observed between CD147 and MMP-9 expression in SDC tissues. The incidences of high expression were 45.71% for CD147 and 51.43% for MMP-9 in 35 SDC tissues, respectively. High expression of CD147 and MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P CD147 = 0.031; P MMP-9 = 0.020) and overall survival (OS) (P CD147 = 0.044; P MMP-9 = 0.013).


CD147 and MMP-9 expression is correlated with invasion, metastasis and shorter PFS/OS of SDC. Patients with high expression of CD147 and MMP-9 had poor prognosis than SDC patients with low expression.


CD147 MMP-9 Salivary duct carcinoma Cancer prognosis Metastasis 



This work was supported by the National Natural Science Foundation of China [Grant Number 81170960] and the Ministry of Education College Doctoral Degree Special Fund [Grant Number 20102307110006].

Conflict of interest

All authors declared that there is no conflict of interest.


  1. Backstrom JR, Tokes ZA (1995) The 84-kDa form of human matrix metalloproteinase-9 degrades substance P and gelatin. J Neurochem 64:1312–1318PubMedCrossRefGoogle Scholar
  2. Bendardaf R, Buhmeida A, Hilska M, Laato M, Syrjänen S (2010) MMP-9 (gelatinase B) expression is associated with disease-free survival and disease-specific survival in colorectal cancer patients. Cancer Invest 28:38–43PubMedCrossRefGoogle Scholar
  3. Biswas C, Zhang Y, DeCastro R et al (1995) The human tumor cell-derived collagenase stimulatory factor (re-named EMMPRIN) is a member of the immunoglobulin super family. Cancer Res 55:434–439PubMedGoogle Scholar
  4. Bourguignon L, Gunja-Smith Z, Iida N et al (1998) CD44v (3, 8–10) is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells. J Cell Physiol 176:206–215PubMedCrossRefGoogle Scholar
  5. Butterworth DM, Jones AW, Kotecha B (1992) Salivary duct carcinoma: Report of case and review of the literature. Virchows Arch 420:371–374CrossRefGoogle Scholar
  6. Chen X, Lin J, Kanekura T et al (2006) A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res 66:11323–11330PubMedCrossRefGoogle Scholar
  7. Davidson B, Goldberg I, Berner A et al (2003) EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis 20:161–169PubMedCrossRefGoogle Scholar
  8. Fridman R, Toth M, Pena D, Mobashery S (1995) Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res 55:2548–2555PubMedGoogle Scholar
  9. Guo H, Li R, Zucker S et al (2000) EMMPRIN (CD147), aninducer of matrix metalloproteinase synthesis, also bindsinterstitial collagenase to the tumor cell surface. Cancer Res 60:888–891PubMedGoogle Scholar
  10. Jaehne M, Roeser K, Jaekel T et al (2005) Clinical and immunohistologic typing of salivary duct carcinoma: a report of 50 cases. Cancer 103:2526–2533PubMedCrossRefGoogle Scholar
  11. Ju XZ, Yang JM, Zhou XY et al (2008) EMMPRIN expression as a prognostic factor in radiotherapy of cervical cancer. Clin Cancer Res 14:494–501PubMedCrossRefGoogle Scholar
  12. Juarez J, Clayman G, Nakajima M, Tanabe KK, Saya H, Nicolson GL et al (1993) Role and regulation of expression of 92-kDa type-IV collagenase (MMP-9) in 2 invasive squamous-cell-carcinoma cell lines of the oral cavity. Int J Cancer 55:10–18PubMedCrossRefGoogle Scholar
  13. Kleinsasser O, Klein HJ, Hubner G (1968) Salivary duct carcinoma: a group of salivary gland tumors analogous to mammary duct carcinoma. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 192:100–105PubMedCrossRefGoogle Scholar
  14. Lewis JE, Mckinney BC, Weiland LH, Ferreiro JA, Olsen KD (1996) Salivary duct carcinoma: clinicopathologic and immunohistochemical review of 26 cases. Cancer 77:223–230PubMedCrossRefGoogle Scholar
  15. Lewis JE, Olsen KD, Sebo TJ (2001) Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol 32:596–604PubMedCrossRefGoogle Scholar
  16. Li Z, Ren Y, Wu QC et al (2004) Macrophage migration inhibitory factor enhances neoplastic cell invasion by inducing the expression of matrix metalloproteinase 9 and interleukin-8 in nasopharyngeal carcinoma cell lines. Chin Med J 117:107–114PubMedGoogle Scholar
  17. Li Y, Jing X, Li C et al (2009) HAb18G (CD147), a cancer-associated biomarker and its role in cancer detection. Histopathology 54:677–687PubMedCrossRefGoogle Scholar
  18. Liotta LA, Stetler-Stevenson WG, Steeg PS (1991) Cancer invasion and metastasis: positive and negative regulatory elements. Cancer Invest 9:543–551PubMedCrossRefGoogle Scholar
  19. Liu Z, Li L, Yang ZX et al (2010) Research article Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer 10:270PubMedGoogle Scholar
  20. Lukkaa H, Klemi P, Hirsimaki P et al (2008) Matrix metalloproteinase (MMP)-1, -9 and -13 as prognostic factors in salivary gland cancer. Acta Otolaryngol 128:482–490CrossRefGoogle Scholar
  21. Masunaga R, Kohno H, Dhar DK, Ohno S, Shibakita M, Kinugasa S, Yoshimura H, Tachibana M, Kubota H, Nagasue N (2000) Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res 6:4064–4068PubMedGoogle Scholar
  22. Mira E, Lacalle RA, Buesa JM et al (2004) Secreted MMP9 promotes angiogenesis more efficiently than constitutive active MMP9 bound to the tumor cell surface. J Cell Sci 117:1847–1857PubMedCrossRefGoogle Scholar
  23. Nakajima M, Welch DR, Belloni PN, Nicolson GL (1987) Degradation of basement membrane type IV collagen and lung subendothelialmatrix by rat mammary adenocarcinoma cell clones of differing metastatic potentials. Cancer Res 47:4869–4876PubMedGoogle Scholar
  24. Overall C, López-Otín C (2002) Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer 2:657–672PubMedCrossRefGoogle Scholar
  25. Ramos-DeSimone N, Hahn-Dantona E, Sipley J et al (1999) Activation of matrix metalloprotease-9 (MMP-9) viaa converting Plasmin/Stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem 274:13066–13076PubMedCrossRefGoogle Scholar
  26. Rao JS, Ra C, Gondi C et al (2005) Inhibition of invasion, angiogenesis, tumor growth, and metastasis by adenovirus-mediated transfer of antisense uPAR and MMP-9 in non-small cell lung cancer cells. Mol Cancer Ther 4:1399–1408PubMedCrossRefGoogle Scholar
  27. Sienel W, Hellers J, Morresi-Hauf A, Lichtinghagen R, Mutschler W, Jochum M, Klein C, Passlick B, Pantel K (2003) Prognostic impact of matrix metalloproteinase-9 in operable non-small cell lung cancer. Int J Cancer 103:647–651PubMedCrossRefGoogle Scholar
  28. Suzuki S, Sato M, Senoo H, Ishikawa K (2004) Direct cell–cell interaction enhances pro-MMP-2 production and activation in co-culture of laryngeal cancer cells and Broblasts: involvement EMMPRIN Mt1-MMP. Exp Cell Res 293:259–266PubMedCrossRefGoogle Scholar
  29. Tang J, Zhou HW, Jiang JL, Yang XM et al (2007) ßig-h3 is involved in the HAb18G/CD147-mediated metastasis process in human hepatoma cells. Exp Biol Med 232:344–352Google Scholar
  30. Tanioka Y, Yoshida T, Yagawa T, Saiki Y, Takeo S, Harada T, Okazawa T, Yanai H, Okita K (2003) Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer. Br J Cancer 89:2116–2121PubMedCrossRefGoogle Scholar
  31. Toole BP (2003) Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function. Curr Top Dev Biol 54:371–389PubMedCrossRefGoogle Scholar
  32. Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536PubMedCrossRefGoogle Scholar
  33. Wang S, Zhou J, Wang XY, Hao JM, Chen JZ, Zhang XM, Jin H, Liu L, Zhang YF, Liu J et al (2009) Down-regulated expression of SATB2 is associated with metastasis and poor prognosis in colorectal cancer. J Pathol 219:114–122PubMedCrossRefGoogle Scholar
  34. Xu J, Shen ZY, Chen XG et al (2007) A randomized controlled trial of Licartin for preventing hepatoma recurrence after liver transplantation. Hepatology 45:269–276PubMedCrossRefGoogle Scholar
  35. Yu WW, Liu JH, Xiong XL et al (2009) Expression of MMP-9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Pract 205:709–715PubMedCrossRefGoogle Scholar
  36. Zhang Q, Chen XG, Zhou J et al (2006) CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients. Cancer Biol Ther 5:808–814PubMedCrossRefGoogle Scholar
  37. Zhang Q, Zhou J, Ku XM et al (2007) Expression of CD147 as a significant unfavorable prognostic factor in hepatocellular carcinoma. Eur J Cancer Prev 16:196–202PubMedCrossRefGoogle Scholar
  38. Zucker HymowitzM, Rollo EE et al (2001) Tumorigenicpotential of extracellular matrix metalloproteinase inducer. Am J Pathol 158:1921–1928PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Songlin Piao
    • 1
  • Shu Zhao
    • 2
  • Fulin Guo
    • 1
  • Jie Xue
    • 1
  • Guodong Yao
    • 3
  • Zhili Wei
    • 4
  • Qi Huang
    • 5
  • Yao Sun
    • 6
  • Bin Zhang
    • 4
    • 6
  1. 1.Department of Oral and Maxillofacial SurgeryThe First Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of Medical OncologyThe Third Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  3. 3.Department of Medical PathologyThe Third Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  4. 4.Department of Oral and Maxillofacial SurgeryThe Second Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  5. 5.Center of MorphologyHarbin Medical UniversityHarbinPeople’s Republic of China
  6. 6.Hard Tissue LabThe Second Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China

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