Skip to main content

Advertisement

SpringerLink
Log in

EMMPRIN in gynecologic cancers: pathologic and therapeutic aspects

  • Review
  • Published:
Tumor Biology

Abstract

The highly glycosylated transmembrane protein extracellular matrix metalloproteinase inducer (EMMPRIN) is associated with several pathological conditions, including various types of cancers. In different gynecological malignancies, such as ovarian, cervical, and endometrial cancers, EMMPRIN plays significant roles in cell adhesion modulation, tumor growth, invasion, angiogenesis, and metastasis by inducing the production of various molecules, including matrix metalloproteinases and vascular endothelial growth factor. Because of its high level of expression, EMMPRIN can possibly be used as a diagnostic marker of gynecological cancers. Recent studies have showed that targeting EMMPRIN, especially by RNA interference (RNAi) technology, has promising therapeutic potential in basic research on gynecological cancer treatments, which make a platform for the future clinical success. This review study focused on the association of EMMPRIN in gynecological cancers in the perspectives of pathogenesis, diagnosis, and therapeutics.

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

Similar content being viewed by others

References

  1. Monteiro LS, Delgado ML, Ricardo S, Garcez F, do Amaral B, Pacheco JJ, et al. EMMPRIN expression in oral squamous cell carcinomas: correlation with tumor proliferation and patient survival. Biomed Res Int. 2014;2014:905680.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Saxena DK, Oh-Oka T, Kadomatsu K, Muramatsu T, Toshimori K. Behaviour of a sperm surface transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice. Reproduction. 2002;123:435–44.

    Article  CAS  PubMed  Google Scholar 

  3. Xiong L, Edwards 3rd CK, Zhou L. The biological function and clinical utilization of CD147 in human diseases: a review of the current scientific literature. Int J Mol Sci. 2014;15:17411–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Iacono KT, Brown AL, Greene MI, Saouaf SJ. CD147 immunoglobulin superfamily receptor function and role in pathology. Exp Mol Pathol. 2007;83:283–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yurchenko V, Constant S, Bukrinsky M. Dealing with the family: CD147 interactions with cyclophilins. Immunology. 2006;117:301–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hanna SM, Kirk P, Holt OJ, Puklavec MJ, Brown MH, Barclay AN. A novel form of the membrane protein CD147 that contains an extra Ig-like domain and interacts homophilically. BMC Biochem. 2003;4:17.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Huang Z, Tan N, Guo W, Wang L, Li H, Zhang T, et al. Overexpression of EMMPRIN isoform 2 is associated with head and neck cancer metastasis. PLoS One. 2014;9, e91596.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ochrietor JD, Moroz TP, van Ekeris L, Clamp MF, Jefferson SC, deCarvalho AC, et al. Retina-specific expression of 5A11/Basigin-2, a member of the immunoglobulin gene superfamily. Invest Ophthalmol Vis Sci. 2003;44:4086–96.

    Article  PubMed  Google Scholar 

  9. Belton Jr RJ, Chen L, Mesquita FS, Nowak RA. Basigin-2 is a cell surface receptor for soluble basigin ligand. J Biol Chem. 2008;283:17805–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Toole BP. Emmprin (CD147), a cell surface regulator of matrix metalloproteinase production and function. Curr Top Dev Biol. 2003;54:371–89.

    Article  CAS  PubMed  Google Scholar 

  11. Yao H, Teng Y, Sun Q, Xu J, Chen YT, Hou N, et al. Important functional roles of basigin in thymocyte development and T cell activation. Int J Biol Sci. 2013;10:43–52.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Zhou XM, Zhang H, Han X. Role of epithelial to mesenchymal transition proteins in gynecological cancers: pathological and therapeutic perspectives. Tumour Biol. 2014;35:9523–30.

    Article  CAS  PubMed  Google Scholar 

  13. Jeong HM, Kwon MJ, Shin YK. Overexpression of cancer-associated genes via epigenetic derepression mechanisms in gynecologic cancer. Front Oncol. 2014;4:12.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  15. Tania M, Khan MA, Song Y. Association of lipid metabolism with ovarian cancer. Curr Oncol. 2010;17:6–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384:1376–88.

    Article  PubMed  Google Scholar 

  17. Tania M, Khan MA, Zhang H, Li J, Song Y. Autotaxin: a protein with two faces. Biochem Biophys Res Commun. 2010;401:493–7.

    Article  CAS  PubMed  Google Scholar 

  18. Morgan Jr RJ, Alvarez RD, Armstrong DK, Boston B, Burger RA, Chen LM, et al. Epithelial ovarian cancer. J Natl Compr Cancer Netw. 2011;9:82–113.

    Google Scholar 

  19. Rossing MA, Wicklund KG, Cushing-Haugen KL, Weiss NS. Predictive value of symptoms for early detection of ovarian cancer. J Natl Cancer Inst. 2010;102:222–9.

    Article  PubMed  PubMed Central  Google Scholar 

  20. du Bois A, Lück HJ, Meier W, Adams HP, Möbus V, Costa S, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003;95:1320–9.

    Article  PubMed  Google Scholar 

  21. Slomiany MG, Dai L, Tolliver LB, Grass GD, Zeng Y, Toole BP. Inhibition of functional hyaluronan-CD44 interactions in CD133-positive primary human ovarian carcinoma cells by small hyaluronan oligosaccharides. Clin Cancer Res. 2009;15:7593–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Canavan TP, Doshi NR. Cervical cancer. Am Fam Physician. 2000;61:1369–76.

    CAS  PubMed  Google Scholar 

  23. Armstrong EP. Prophylaxis of cervical cancer and related cervical disease: a review of the cost-effectiveness of vaccination against oncogenic HPV types. J Manag Care Pharm. 2010;16:217–30.

    PubMed  Google Scholar 

  24. Jiang B, Xiao S, Khan MA, Xue M. Defective antioxidant systems in cervical cancer. Tumour Biol. 2013;34:2003–9.

    Article  CAS  PubMed  Google Scholar 

  25. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011;378:1461–84.

    Article  PubMed  Google Scholar 

  26. Colombo N, Carinelli S, Colombo A, Marini C, Rollo D, Sessa C, et al. Cervical cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii27–32.

    PubMed  Google Scholar 

  27. Waggoner SE. Cervical cancer. Lancet. 2003;361:2217–25.

    Article  PubMed  Google Scholar 

  28. Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C, et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:vi33–8.

    Article  PubMed  Google Scholar 

  29. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2095–128.

    Article  PubMed  Google Scholar 

  30. Pessoa JN, Freitas AC, Guimaraes RA, Lima J, Dos Reis HL, Filho AC. Endometrial assessment: when is it necessary? J Clin Med Res. 2014;6(1):21–5.

    PubMed  Google Scholar 

  31. Bakkum-Gamez JN, Gonzalez-Bosquet J, Laack NN, Mariani A, Dowdy SC. Current issues in the management of endometrial cancer. Mayo Clin Proc. 2008;83:97–112.

    Article  PubMed  Google Scholar 

  32. Kurra V, Krajewski KM, Jagannathan J, Giardino A, Berlin S, Ramaiya N. Typical and atypical metastatic sites of recurrent endometrial carcinoma. Cancer Imaging. 2013;13:113–22.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Vale CL, Tierney J, Bull SJ, Symonds PR. Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma. Cochrane Database Syst Rev. 2012;8, CD003915.

    Google Scholar 

  34. Galaal K, Al Moundhri M, Bryant A, Lopes AD, Lawrie TA. Adjuvant chemotherapy for advanced endometrial cancer. Cochrane Database Syst Rev. 2014;5, CD010681.

    Google Scholar 

  35. Zheng HC, Takahashi H, Murai Y, Cui ZG, Nomoto K, Miwa S, et al. Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer. 2006;95:1371–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yan L, Zucker S, Toole BP. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression. Thromb Haemost. 2005;93:199–204.

    CAS  PubMed  Google Scholar 

  37. Yang H, Chen B. CD147 in ovarian and other cancers. Int J Gynecol Cancer. 2013;23:2–8.

    Article  PubMed  Google Scholar 

  38. Davidson B, Goldberg I, Berner A, Kristensen GB, Reich R. EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis. 2003;20:161–9.

    Article  CAS  PubMed  Google Scholar 

  39. Feng L, Zhu S, Zhang Y, Li Y, Gong L, Lan M, et al. Expression and clinical significance of HAb18G/CD147 in malignant tumors. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2013;29:958–61.

    CAS  PubMed  Google Scholar 

  40. Jin JS, Yao CW, Loh SH, Cheng MF, Hsieh DS, Bai CY. Increasing expression of extracellular matrix metalloprotease inducer in ovary tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters. Int J Gynecol Pathol. 2006;25:140–6.

    Article  PubMed  Google Scholar 

  41. Zhao Y, Chen S, Gou WF, Niu ZF, Zhao S, Xiao LJ, et al. The role of EMMPRIN expression in ovarian epithelial carcinomas. Cell Cycle. 2013;12:2899–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Szubert S, Szpurek D, Moszynski R, Nowicki M, Frankowski A, Sajdak S, et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer. J Cancer Res Clin Oncol. 2014;140:361–9.

    Article  CAS  PubMed  Google Scholar 

  43. Sato T, Ota T, Watanabe M, Imada K, Nomizu M, Ito A. Identification of an active site of EMMPRIN for the augmentation of matrix metalloproteinase-1 and -3 expression in a co-culture of human uterine cervical carcinoma cells and fibroblasts. Gynecol Oncol. 2009;114:337–42.

    Article  CAS  PubMed  Google Scholar 

  44. Yu W, Liu J, Xiong X, Ai Y, Wang H. Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Pract. 2009;205:709–15.

    Article  CAS  PubMed  Google Scholar 

  45. Wu Y, Zhou X, Zheng PS. Involvement of CD147 isoform-4 in the proliferation of SiHa cells: a possible molecular mechanism of cervical cancer. Oncol Rep. 2011;26:717–24.

    CAS  PubMed  Google Scholar 

  46. Meng Y, Wei L, Wang J. Monitoring gene expression profile changes in endometrial cancer using cDNA microarray technology. Zhonghua Yi Xue Za Zhi. 2001;81:665–8.

    CAS  PubMed  Google Scholar 

  47. Nakamura K, Kodama J, Hongo A, Hiramatsu Y. Role of emmprin in endometrial cancer. BMC Cancer. 2012;12:191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gabison EE, Hoang-Xuan T, Mauviel A, Menashi S. EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie. 2005;87:361–8.

    Article  CAS  PubMed  Google Scholar 

  49. Caudroy S, Polette M, Nawrocki-Raby B, Cao J, Toole BP, Zucker S, et al. EMMPRIN-mediated MMP regulation in tumor and endothelial cells. Clin Exp Metastasis. 2002;19:697–702.

    Article  CAS  PubMed  Google Scholar 

  50. Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res. 2005;65:3193–9.

    CAS  PubMed  Google Scholar 

  51. Bougatef F, Quemener C, Kellouche S, Naïmi B, Podgorniak MP, Millot G, Gabison EE, Calvo F, Dosquet C, Lebbé C, Menashi S, Mourah S. EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2alpha-mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2. Blood. 2009;114:5547–56.

  52. Chen Y, Zhang H, Gou X, Horikawa Y, Xing J, Chen Z. Upregulation of HAb18G/CD147 in activated human umbilical vein endothelial cells enhances the angiogenesis. Cancer Lett. 2009;278:113–21.

    Article  CAS  PubMed  Google Scholar 

  53. Millimaggi D, Mari M, D’Ascenzo S, Carosa E, Jannini EA, Zucker S, et al. Tumor vesicle-associated CD147 modulates the angiogenic capability of endothelial cells. Neoplasia. 2007;9:349–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yang H, Zou W, Chen B. Overexpression of CD147 in ovarian cancer is initiated by the hypoxic microenvironment. Cell Biol Int. 2013;37:1139–42.

    Article  CAS  PubMed  Google Scholar 

  55. Fukuoka M, Hamasaki M, Koga K, Hayashi H, Aoki M, Kawarabayashi T, et al. Expression patterns of emmprin and monocarboxylate transporter-1 in ovarian epithelial tumors. Virchows Arch. 2012;461:457–66.

    Article  CAS  PubMed  Google Scholar 

  56. Chen H, Wang L, Beretov J, Hao J, Xiao W, Li Y. Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression. Clin Exp Metastasis. 2010;27:557–69.

    Article  CAS  PubMed  Google Scholar 

  57. Pinheiro C, Longatto-Filho A, Pereira SM, Etlinger D, Moreira MA, Jubé LF, et al. Monocarboxylate transporters 1 and 4 are associated with CD147 in cervical carcinoma. Dis Markers. 2009;26:97–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sier CF, Zuidwijk K, Zijlmans HJ, Hanemaaijer R, Mulder-Stapel AA, Prins FA, et al. EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinoma. Int J Cancer. 2006;118:2991–8.

    Article  CAS  PubMed  Google Scholar 

  59. Zhang F, Zeng YL, Zhang XG, Chen WJ, Yang R, Li SJ. RNA interference targeting extracellular matrix metalloproteinase inducer (CD147) inhibits growth and increases chemosensitivity in human cervical cancer cells. Eur J Gynaecol Oncol. 2013;34:429–35.

    CAS  PubMed  Google Scholar 

  60. Pils S, Joura EA, Winter MP, Shrestha A, Jaeger-Lansky A, Ott J. What do women with gynecologic cancer know about HPV and their individual disease? A pilot study. BMC Cancer. 2014;14:388.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Zou W, Yang H, Hou X, Zhang W, Chen B, Xin X. Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to paclitaxel in HO-8910pm cells. Cancer Lett. 2007;248:211–8.

    Article  CAS  PubMed  Google Scholar 

  62. Zhang X, Liu P, Zhang B, Wang A, Yang M. Role of STAT3 decoy oligodeoxynucleotides on cell invasion and chemosensitivity in human epithelial ovarian cancer cells. Cancer Genet Cytogenet. 2010;197:46–53.

    Article  CAS  PubMed  Google Scholar 

  63. Zhao SH, Wang Y, Wen L, Zhai ZB, Ai ZH, Yao NL, et al. Basigin-2 is the predominant basigin isoform that promotes tumor cell migration and invasion and correlates with poor prognosis in epithelial ovarian cancer. J Transl Med. 2013;11:92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Gao J, Hu Z, Liu J, Liu D, Wang Y, Cai M, et al. Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance. Med Oncol. 2014;31:920.

    Article  PubMed  Google Scholar 

  65. Sato T, Watanabe M, Hashimoto K, Ota T, Akimoto N, Imada K, et al. A novel functional site of extracellular matrix metalloproteinase inducer (EMMPRIN) that limits the migration of human uterine cervical carcinoma cells. Int J Oncol. 2012;40:236–42.

    CAS  PubMed  Google Scholar 

  66. Fan X, Wu W, Shi H, Han J. RNA interference targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells by downregulating MMP-9. Cell Biol Int. 2013;37:737–41.

    Article  CAS  PubMed  Google Scholar 

  67. Huang XQ, Chen X, Xie XX, Zhou Q, Li K, Li S, et al. Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7:1651–66.

    PubMed  PubMed Central  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Gynecology, Cangzhou Central Hospital, Cangzhou, 061001, China

    Dan-tong Liu

Authors
  1. Dan-tong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dan-tong Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Dt. EMMPRIN in gynecologic cancers: pathologic and therapeutic aspects. Tumor Biol. 36, 4883–4888 (2015). https://doi.org/10.1007/s13277-015-3544-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-3544-6

Keywords

Search

Navigation