ABB  Vol.3 No.1 , February 2012
Matrix metalloproteinase-2 and -9 secretion by the human JAR choriocarcinoma cell line is stimulated by TNF-α
Author(s) Benoît Chénais
The JAR choriocarcinoma cell line share many of the characteristics of early placental trophoblast cells including the invasion properties. Matrix metallo-proteinases (MMPs), the main actors of matrix proteolysis, are involved in normal invasion as well as in the invasive character of tumor cells and the metastase formation. Tumor necrosis factor-α (TNF-α) is present in the placental environment and TNF-α levels are elevated in some placental pathologies. In the present work, we addressed whether TNF-α is a modulator of JAR cell MMP secretion. Following TNF-α stimulation, zymographic analysis showed the increased secretion of the active form of MMP-2 and to a lesser extent proMMP-2 and MMP-9. In addition, MMP-2 gene expression only increased slightly whereas MMP-9 and TIMP-1 transcripts were undetectable. This suggests that TNF-α may modulate the secretion of MMPs independently of MMP gene expression control.

Cite this paper
Chénais, B. (2012) Matrix metalloproteinase-2 and -9 secretion by the human JAR choriocarcinoma cell line is stimulated by TNF-α. Advances in Bioscience and Biotechnology, 3, 51-56. doi: 10.4236/abb.2012.31009.
[1]   Bamberger, A.M., et al. (2004) Expression pattern of the activating protein-1 family of transcription factors in the human placenta. Molecular Human Reproduction, 10, 223-228. doi:10.1093/molehr/gah011

[2]   Hohn, H.P., Linke, M., Ugele, B. and Denker, H.W. (1998) Differentiation markers and invasiveness: Discordant regulation in normal trophoblast and choriocarcinoma cells. Experimental Cell Research, 244, 249-258. doi:10.1006/excr.1998.4184

[3]   White, T.E., et al. (1988) Human choriocarcinoma (JAR) cells grown as multicellular spheroids. Placenta, 9, 583- 598. doi:10.1016/0143-4004(88)90002-1

[4]   Grümmer, R., Hohn, H.P., Mareel M.M. and Denker, H.W. (1994) Adhesion and invasion of three human choriocarcinoma cell lines into human endometrium in a three- dimensional organ culture system. Placenta, 15, 411-429. doi:10.1016/0143-4004(94)90008-6

[5]   Chaddha, V., Viero, S., Huppertz, B. and Kingdom, J. (2004) Developmental biology of the placenta and the origins of placental insufficiency. Seminars in Fetal and Neonatal Medicine, 9, 357-369. doi:10.1016/j.siny.2004.03.006

[6]   Kaufmann, P., Black, S. and Huppertz, B. (2003) Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biology of Reproduction, 69, 1-7. doi:10.1095/biolreprod.102.014977

[7]   Goldman-Wohl, D. and Yagel, S. (2002) Regulation of trophoblast invasion: From normal implantation to preeclampsia. Molecular and Cellular Endocrinology, 187, 233-238. doi:10.1016/S0303-7207(01)00687-6

[8]   Fisher, S.J. (2004) The placental problem: Linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia. Reproductive Biology and Endocrinology, 2, 53. doi:10.1186/1477-7827-2-53

[9]   Chakraborty, C., Gleeson, L.M., McKinnon, T. and Lala, P.K. (2002) Regulation of human trophoblast migration and invasiveness. Canadian Journal of Physiology and Pharmacology, 80, 116-124. doi:10.1139/y02-016

[10]   Argiles, J.M., Carbo, N. and Lopez-Soriano, F.J. (1997) TNF and pregnancy: The paradigm of a complex interacttion. Cytokine and Growth Factor Reviews, 8,181-188. doi:10.1016/S1359-6101(97)00012-9

[11]   Schafer-Somi, S. (2003) Cytokines during early pregnancy of mammals: A review. Animal Reproduction Science, 75, 73-94. doi:10.1016/S0378-4320(02)00222-1

[12]   Conrad, K.P. and Benyo, D.F. (1997) Placental cytokines and the pathogenesis of preeclampsia. American Journal of Reproductive Immunology, 37, 240-249. doi:10.1111/j.1600-0897.1997.tb00222.x

[13]   Holcberg, G., et al. (2001) Increased production of tumor necrosis factor-α TNF-α by IUGR human placentae. European Journal of Obstetrics & Gynecology and Reproductive Biology, 94, 69-72. doi:10.1016/S0301-2115(00)00321-3

[14]   Cohen, M., Meisser, A., Haenggeli, L. and Bischof P. (2006) Involvement of MAPK pathway in TNF-alpha-induced MMP-9 expression in human trophoblastic cells. Molecular Human Reproduction, 12, 225-232. doi:10.1093/molehr/gal023

[15]   Lockwood C.J., et al. (2008) Matrix Metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual Cells. Biology of Reproduction, 78, 1064-1072. doi:10.1095/biolreprod.107.063743

[16]   Renaud, S.J., et al. (2005) Activated macrophages inhibit human cytotrophoblast invasiveness in vitro. Biology of Reproduction, 73, 237-243. doi:10.1095/biolreprod.104.038000

[17]   Otun H.A., et al. (2011) Effect of tumour necrosis factor-α in combination with interferon-γ on first trimester extravillous trophoblast invasion. Journal of Reproductive Immunology, 2011, 88, 1-11. doi:10.1016/j.jri.2010.10.003

[18]   Phillips, T.A., Ni, J. and Hunt, J.S. (2001) Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines. Placenta, 22, 663-672. doi:10.1053/plac.2001.0703

[19]   Westermarck, J. and Kahari, V.M. (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB Journal, 13, 781-792.

[20]   Brew, K., Dinakarpandian, D. and Nagase, H. (2000) The tissue inhibitors of metalloproteinases (TIMPs): An ancient family with structural and functional diversity. Biochimica et Biophysica Acta, 1477, 267-283. doi:10.1016/S0167-4838(99)00279-4

[21]   Myers, J.E., et al., (2005) MMP-2 levels are elevated in the plasma of women who subsequently develop preeclampsia. Hypertension in Pregnancy, 24, 103-115. doi:10.1081/PRG-200059836

[22]   Shokry, M., Omran, O.M., Hassan, H.I., Elsedfy, G.O. and Hussein, M.R. (2009) Expression of matrix metalloproteinases 2 and 9 in human trophoblasts of normal and preeclamptic placentas: preliminary findings. Experimental and Molecular Pathology, 87, 219-225. doi:10.1016/j.yexmp.2009.08.001

[23]   Dimo, B., et al., (2011) Comparative study of the immuno-histochemical expression of tissue inhibitors of metallo-proteinases 1 and 2 between clearly invasive carcinomas and “in situ” trophoblast invasion. Medical Oncology, in press.

[24]   Morgan, M., Kniss, D. and McDonnell, S. (1998) Expression of metalloproteinases and their inhibitors in human trophoblast continuous cell lines. Experimental Cell Research, 242, 18-26. doi:10.1006/excr.1997.3929

[25]   Singh M., et al. (2011) Matrix metalloproteinases and their inhibitors and inducer in gestational trophoblastic diseases and normal placenta. Gynecologic Oncology, 122, 178-182. doi:10.1016/j.ygyno.2011.03.025

[26]   Staun-Ram, E., Goldman, S., Gabarin, D. and Shalev, E. (2004) Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion. Reproductive Biology and Endocrinology, 2, 59. doi:10.1186/1477-7827-2-59

[27]   Schr?pfer, A., et al. (2010) Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines. BMC Cancer, 10, 553. doi:10.1186/1471-2407-10-553

[28]   Pattillo, R.A., Ruckert, A.C., Hussa, R.O., Bernstein, R. and Delfs, E. (1971) The JAR cell line, continuous human multihormone production and controls. In Vitro, 6, 398.

[29]   Heussen, C. and Dowdle, E.B. (1980) Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Analytical Biochemistry, 102, 196-202.

[30]   Richard, D., Hollender, P. and Chénais B. (2002) Butyric acid increases invasiveness of HL-60 leukemia cells: role of reactive oxygen species. FEBS Letters, 518, 159-163. doi:10.1016/S0014-5793(02)02690-X

[31]   Richard, D., Hollender, P. and Chénais, B. (2002) Involvement of reactive oxygen species in aclarubicin-induced differentiation and invasiveness of HL-60 leukemia cells. International Journal of Oncology, 21, 393-399.

[32]   Moll, U.M., Youngleib, G.L., Rosinski, K.B. and Quigley, J.P. (1990) Tumor promoter-stimulated Mr 92,000 gelatinase secreted by normal and malignant human cells: Isolation and characterization of the enzyme from HT1080 tumor cells. Cancer Research, 50, 6162-6170.

[33]   Chénais, B., et al. (2005) Functional and placental expression analysis of the human NRF3 transcription factor. Molecular Endocrinology, 19, 125-137.

[34]   Staff, A.C., Ranheim, T., Henriksen, T. and Halvorsen, B. (2000) 8-Iso-prostaglandin f(2alpha) reduces trophoblast invasion and matrix metalloproteinase activity. Hypertension, 35, 1307-1313.

[35]   Mandl, M., Haas, J., Bischof, P., N?hammer, G. and Desoye, G. (2002) Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models. Histochemical Cell Biology, 117, 391-399. doi:10.1007/s00418-002-0403-5

[36]   Hiden U., et al. (2007) The first trimester human trophoblast cell line ACH-3P: A novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations—TNF-α stimulates MMP15 expression. BMC Developmental Biology, 7, 137. doi:10.1186/1471-213X-7-137

[37]   Jenkins C., et al. (2000) Evidence of a T(H) 1 type response associated with recurrent miscarriage. Fertility and Sterility, 73, 1206-1208. doi:10.1016/S0015-0282(00)00517-3

[38]   Mjihdi, A., Truyens, C., Detournay, O. and Carlier Y. (2004) Systemic and placental productions of tumor necrosis factor contribute to induce fetal mortality in mice acutely infected with Trypanosoma cruzi. Experimental Parasitology, 107, 58-64. doi:10.1016/j.exppara.2004.03.016

[39]   Kim S., et al. (2005) Interferon-gamma promotes abortion due to Brucella infection in pregnant mice. BMC Microbiology, 5, 22. doi:10.1186/1471-2180-5-22

[40]   Scaife, P.J., Bulmer, J.N., Robson, S.C., Innes, B.A. and Searle, R.F. (2006) Effector activity of decidual CD8+ T lymphocytes in early human pregnancy. Biology of Reproduction, 75, 562-567. doi:10.1095/biolreprod.106.052654

[41]   Hanna, J. and Mandelboim O. (2007) When killers become helpers. Trends in Immunology, 28, 201-206. doi:10.1016/

[42]   Baud, V. and Karin, M. (2001) Signal transduction by tumor necrosis factor and its relatives. Trends in Cell Biology, 11, 372-377. doi:10.1016/S0962-8924(01)02064-5

[43]   Wajant, H., Pfizenmaier, K. and Scheurich, P. (2003) Tumor necrosis factor signalling. Cell Death and Differentiation, 10, 45-65. doi:10.1038/sj.cdd.4401189

[44]   Aggarwal, B.B., Shishodia, S., Sandur, S.K., Pandey M.K. and Sethi, G. (2006) Inflammation and cancer: How hot is the link? Biochemical Pharmacology, 72, 1605-1621. doi:10.1016/j.bcp.2006.06.029

[45]   Goldman, S., Lovett, D.H. and Shalev, E. (2009) Mechanisms of matrix metalloproteinase-2 (MMP-2) transcriptional repression by progesterone in JAR choriocarcinoma cells. Reproductive Biology and Endocrinology, 7, 41. doi:10.1186/1477-7827-7-41