Chinese Science Bulletin

, Volume 50, Issue 12, pp 1169–1173 | Cite as

Matrix metalloproteinases (MMPs) and trophoblast invasion

  • Jing Li
  • Tianfu Zhao
  • Enkui Duan


MMPs and their natural tissue inhibitors TIMPs are crucial in coordinated breakdown and remodeling of the extracellular matrix (ECM) in physiological and pathological situations. Placentation is a key event of pregnancy in which MMPs/TIMPs system plays important roles in regulating the extravillus cytotrophoblast (EVTs) invasion. This paper focuses on expression patterns and regulatory mechanisms of MMPs/TIMPs family members during the process of placentation. Their implications in curing pregnancy-related diseases are also discussed.


MMPs TIMPs placenta trophoblast invasion extracellular matrix (ECM) 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kerkela, E., Saarialho-Kere, U., Matrix metalloproteinases in tumor progression: Focus on basal and squamous cell skin cancer, Exp. Dermatol., 2003, 12(2): 109–125.CrossRefGoogle Scholar
  2. 2.
    Leeman, M. F., Curran, S., Murray, G. I., New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression, J. Pathol., 2003, 201(4): 528–534.CrossRefGoogle Scholar
  3. 3.
    Hojilla, C. V., Mohammed, F. F., Khokha, R., Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development, Br. J. Cancer, 2003, 89(10): 1817–1821.CrossRefGoogle Scholar
  4. 4.
    Yoon, S. O., Park, S. J., Yun, C. H. et al., Roles of matrix metallo-proteinases in tumor metastasis and angiogenesis, J. Biochem. Mol. Biol., 2003, 36(1): 128–137.Google Scholar
  5. 5.
    Zhou, Y., Genbacev, O., Fisher, S. J., The human placenta remodels the uterus by using a combination of molecules that govern vasculogenesis or leukocyte extravasation, Ann. N. Y. Acad. Sci., 2003, 995: 73–83.CrossRefGoogle Scholar
  6. 6.
    Huppertz, B., Kertschanska, S., Demir, A. Y. et al., Immunohisto-chemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta, Cell Tissue Res., 1998, 291(1): 133–148.CrossRefGoogle Scholar
  7. 7.
    Isaka, K., Usuda, S., Ito, H. et al., Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts, Placenta, 2003, 24(1): 53–64.CrossRefGoogle Scholar
  8. 8.
    Zhang, J., Cao, Y. J., Zhao, Y. G. et al., Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3, Mol. Hum. Reprod., 2002, 8(7): 659–666.CrossRefGoogle Scholar
  9. 9.
    Zhang, J., Cao, Y. J., Liu, W. M. et al., Expression of matrix metalloproteinase-28 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3, Chinese Science Bulletin, 2002, 47(9): 732–736.CrossRefGoogle Scholar
  10. 10.
    Zhao, Y. G., Xiao, A. Z., Newcomer, R. G. et al., Activation of pro-gelatinase B by endometase/matrilysin-2 promotes invasion of human prostate cancer cells, J. Biol. Chem., 2003, 278(17): 15056–15064.CrossRefGoogle Scholar
  11. 11.
    Yamamoto, H., Vinitketkumnuen, A., Adachi, Y. et al., Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma, Carcinogenesis, 2004, 25(12): 2353–2360.CrossRefGoogle Scholar
  12. 12.
    Tie, G. D., Tian, Y. Q., Chen, S. Y. et al., Regulation of mouse blastocyst adhesion, outgrowth and matrix metalloproteinase-2 by focal adhesion kinase, Chinese Science Bulletin, 2003, 48(5): 475–479.Google Scholar
  13. 13.
    Shen, Z., Zhao, X. X., Cao, Y. J. et al., Regulation of mouse blastocyst adhesion, outgrowth and secretion of matrix metalloproteinase-2 by cGMP and nitric oxidein vitro, Chinese Science Bulletin, 2004, 49(11): 1142–1145.CrossRefGoogle Scholar
  14. 14.
    Kharfi, A., Giguere, Y., Sapin, V. et al., Trophoblastic remodeling in normal and preeclamptic pregnancies: Implication of cytokines, Clin. Biochem., 2003, 36(5): 323–331.CrossRefGoogle Scholar
  15. 15.
    Anteby, E. Y., Greenfield, C., Natanson-Yaron, S. et al., Vascular endothelial growth factor, epidermal growth factor and fibroblast growth factor −4 and −10 stimulate trophoblast plasminogen activator system and metalloproteinase-9, Mol. Hum. Reprod., 2004, 10(4): 229–235.CrossRefGoogle Scholar
  16. 16.
    Zhang, J., Cao, Y. J., Li, F. Y. et al., Effects of fibronectin, VEGF and angiostatin on the expression of MMPs through different signaling pathways in the JEG-3 cells, Am. J. Reprod. Immunol., 2003, 50(4): 273–285.CrossRefGoogle Scholar
  17. 17.
    Librach, C. L., Feigenbaum, S. L., Bass, K. E. et al., Interleukin-1 beta regulates human cytotrophoblast metalloproteinase activity and invasionin vitro, J. Biol. Chem. 1994, 269(25): 17125–17131.Google Scholar
  18. 18.
    Karmakar, S., Das, C., Regulation of trophoblast invasion by IL-1beta and TGF-beta1, Am. J. Reprod. Immunol., 2002, 48(4): 210–219.CrossRefGoogle Scholar
  19. 19.
    Meisser, A., Chardonnens, D., Campana, A. et al., Effects of tumour necrosis factor-alpha, interleukin-1 alpha, macrophage colony stimulating factor and transforming growth factor beta on trophoblastic matrix metalloproteinases, Mol. Hum. Reprod., 1999, 5(3): 252–260.CrossRefGoogle Scholar
  20. 20.
    Meisser, A., Cameo, P., Islami, D. et al., Effects of interleukin-6 (IL-6) on cytotrophoblastic cells, Mol. Hum. Reprod., 1999, 5(11): 1055–1058.CrossRefGoogle Scholar
  21. 21.
    Zygmunt, M., Hahn, D., Kiesenbauer, N. et al., Invasion of cytotrophoblastic (JEG-3) cells is up-regulated by interleukin-15in vitro, Am. J. Reprod. Immunol., 1998, 40(5): 326–331.Google Scholar
  22. 22.
    Bauer, S., Pollheimer, J., Hartmann, J. et al., Tumor necrosis factor-alpha inhibits trophoblast migration through elevation of plasminogen activator inhibitor-1 in first-trimester villous explant cultures, J. Clin. Endocrinol. Metab., 2004, 89(2): 812–822.CrossRefGoogle Scholar
  23. 23.
    Bischof, P., Truong, K., Campana, A., Regulation of trophoblastic gelatinases by proto-oncogenes, Placenta, 2003, 24(2–3): 155–163.CrossRefGoogle Scholar
  24. 24.
    Bischof, P., Meisser, A., Campana, A. et al., Effects of deciduaconditioned medium and insulin-like growth factor binding protein-1 on trophoblastic matrix metalloproteinases and their inhibitors, Placenta, 1998, 19(7): 457–464.CrossRefGoogle Scholar
  25. 25.
    Yamamoto-Tabata, T., McDonagh, S., Chang, H. T. et al., Human cytomegalovirus interleukin-10 downregulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasivenessin vitro, J. Virol., 2004, 78(6): 2831–2840.CrossRefGoogle Scholar
  26. 26.
    Szony, B. J., Bata-Csorgo, Z., Bartfai, G. et al., Interleukin-10 receptors are expressed by basement membrane anchored, alpha(6) integrin(+) cytotrophoblast cells in early human placenta, Mol. Hum. Reprod., 1999, 5(11): 1059–1065.CrossRefGoogle Scholar
  27. 27.
    Malassine, A., Cronier, L., Hormones and human trophoblast differentiation: A review, Endocrine, 2002, 19(1): 3–11.CrossRefGoogle Scholar
  28. 28.
    Yagel, S., Geva-Eldar, T., Solomon, H. et al., High levels of hCG retard first trimester trophoblast invasionin vitro by decreasing uPA and collagenase activities, J. Clin. Endocrinol. Metab., 1993, 77: 1506–1511.CrossRefGoogle Scholar
  29. 29.
    Staff, A. C., Ranheim, T., Henriksen, T. et al., 8-Iso-prostaglandin f (2alpha) reduces trophoblast invasion and matrix metalloproteinase activity, Hypertension, 2000, 35(6): 1307–1313.Google Scholar
  30. 30.
    Castellucci, M., De Matteis, R., Meisse, A. et al., Leptin modulates extracellular matrix molecules and metalloproteinases: Possible implications for trophoblast invasion, Mol. Hum. Reprod., 2000, 6(10): 951–958.CrossRefGoogle Scholar
  31. 31.
    Chou, C. S., Zhu, H., MacCalman, C. D. et al., Regulatory effects of gonadotropin-releasing hormone (GnRH) I and GnRH II on the levels of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 in primary cultures of human extravillous cytotrophoblasts, J. Clin. Endocrinol. Metab., 2003, 88(10): 4781–4790.CrossRefGoogle Scholar
  32. 32.
    Caniggia, I., Lye, S. J., Cross, J. C., Activin is a local regulator of human cytotrophoblast cell differentiation, Endocrinology, 1997, 138(9): 3976–3986.CrossRefGoogle Scholar
  33. 33.
    Genbacev, O., Zhou, Y., Ludlow, J. W. et al., Regulation of human placental development by oxygen tension, Science, 1997, 277(5332): 1669–1672.CrossRefGoogle Scholar
  34. 34.
    Novaro, V., Colman-Lerner, A., Ortega, F. V. et al., Regulation of metalloproteinases by nitric oxide in human trophoblast cells in culture, Reprod. Fertil. Dev., 2001, 13(5–6): 411–420.CrossRefGoogle Scholar
  35. 35.
    Xu, P., Wang, Y., Piao, Y. et al., Effects of matrix proteins on the expression of matrix metalloproteinase−2, −9, and −14 and tissue inhibitors of metalloproteinases in human cytotrophoblast cells during the first trimester, Biol. Reprod., 2001, 65(1): 240–246.CrossRefGoogle Scholar
  36. 36.
    Seiki, M., Membrane-type 1 matrix metalloproteinase: A key enzyme for tumor invasion, Cancer Lett., 2003, 194(1): 1–11.CrossRefGoogle Scholar

Copyright information

© Science in China Press 2005

Authors and Affiliations

  1. 1.State Key Laboratory of Reproductive Biology, Institute of ZoologyChinese Academy of SciencesBeijingChina
  2. 2.Graduate School of the Chinese Academy of SciencesBeijingChina
  3. 3.Department of BiologyBaoding Teacher’s CollegeBaodingChina

Personalised recommendations