Tumor cell and carcinoma-associated fibroblast interaction regulates matrix metalloproteinases and their inhibitors in oral squamous cell carcinoma (original) (raw)

Abstract

Co-culture of periodontal ligament (PDL) fibroblasts and SCC-25 oral squamous carcinoma cells (OSCC), results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs). Paracrin circuits between CAFs and OSCC cells were hypothesized to regulate the gene expression of matrix remodeling enzymes in their co-culture, which was performed for 7 days, followed by analysis of the mRNA/protein expression and activity of metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and other relevant genes. Interleukin1-β, transforming growth factor-β1, fibronectin and αvβ6 integrin have shown to be involved in the regulation of the MMP and TIMP gene expression in co-culture of CAFs and tumor cells. In addition, these cells also cooperated in activation of MMP pro-enzymes. It is particularly interesting that the fibroblast-produced inactive MMP-2 has been activated by the tumor-cell-produced membrane-type 1 matrix metalloproteinase (MT1-MMP). The crosstalk between cancer- and the surrounding fibroblast stromal-cells is essential for the fine tuning of cancer cells invasivity.Summary of the suggested mechanism for the regulation of MMPs and TIMPs in the paracrine interplay between SCC-25 cells and fibroblasts. MMP-9 showed a tumor specific expression, regulated presumably by the fibronectin ITGA5B6 pathway. The ITGA5 was inducible in both SCC-25 and PDL fibroblasts in co-culture, but ITGB6 expression was tumor (SCC-25) specific. Based on a previous report [41], MMP-9 might be activated in the interaction with CD-44, and according to our gelatinase assay results, it remains bound with the tumor cells (A). The results of this study suggest that MMP-2 is secreted in its pro- (inactive-) form by CAFs surrounding the tumor cells, and at a lower extent also by the tumor cells themselves. Activation of MMP-2 either requires MT1-MMP localized on the SCC-25 cancer cells [31], or integrins, where the involvement of αv integrins (ITGA5) is expected (A).MMPs-1, 3 and TIMPs-1, 3 are produced in the PDL fibroblasts, and their expression might be regulated by inflammatory cytokines, including IL1-β produced by SCC-25 cells. The expression of TIMP-1 and TIMP-3 is 20–70-times higher than that of MMPs-1 and 3. The gene expression of MMP-1; 2, TIMP-1 and TIMP-3 was reduced by dexamethasone (DEX) (B).

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.

References (47)

  1. G. Mamelle, J. Pampurik, B. Luboinski, R. Lancar, A. Lusinchi, J. Bosq, Lymph node prognostic factors in head and neck squamous cell carcinomas, Am. J. Surg. 168 (1994) 494-498.
  2. E.F. Hensen, M.J. De Herdt, J.J. Goeman, J. Oosting, V.T. Smit, C.J. Cornelisse, R.J. Baatenburg de Jong, Gene-expression of metastasized versus non-metastasized primary head and neck squamous cell carcinomas: a pathway-based analysis, BMC Cancer 8 (2008) 168.
  3. D.B. Villaret, T. Wang, D. Dillon, J. Xu, D. Sivam, M.A. Cheever, S.G. Reed, Identification of genes overexpressed in head and neck squamous cell carcinoma using a combination of complementary DNA subtraction and microarray analysis, Laryngoscope 110 (2000) 374-381.
  4. A.A. El Badry, A.A. El-Fadle, A.L. El-Balshy, Tissue inhibitor of matrix metalloproteinase-2 in nasopharyngeal carcinoma, MedGenMed 9 (2007) 3.
  5. H. Ruokolainen, P. Paakko, T. Turpeenniemi-Hujanen, Tissue inhibitor of matrix metalloproteinase-1 is prognostic in head and neck squamous cell carcinoma: comparison of the circulating and tissue immunoreactive protein, Clin. Cancer Res. 11 (2005) 3257-3264.
  6. A. Orimo, R.A. Weinberg, Stromal fibroblasts in cancer: a novel tumor-promoting cell type, Cell Cycle 5 (2006) 1597-1601.
  7. K. Higashikawa, S. Yoneda, M. Taki, H. Shigeishi, S. Ono, K. Tobiume, N. Kamata, Gene expression profiling to identify genes associated with high-invasiveness in human squamous cell carcinoma with epithelial-to-mesenchymal transition, Cancer Lett. 264 (2008) 256-264.
  8. P. Paterlini-Brechot, N.L. Benali, Circulating tumor cells (CTC) detection: clinical impact and future directions, Cancer Lett. 253 (2007) 180-204.
  9. K.E. Hoot, J. Lighthall, G. Han, S.L. Lu, A. Li, W. Ju, M. Kulesz- Martin, E. Bottinger, X.J. Wang, Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression, J. Clin. Invest. 118 (2008) 2722-2732.
  10. C. Casarsa, N. Bassani, F. Ambrogi, G. Zabucchi, P. Boracchi, E. Biganzoli, D. Coradini, Epithelial-to-mesenchymal transition, cell polarity and stemness-associated features in malignant pleural mesothelioma, Cancer Lett. 302 (2011) 136-143.
  11. J. Dudas, M. Bitsche, V. Schartinger, C. Falkeis, G.M. Sprinzl, H. Riechelmann, Fibroblasts produce brain-derived neurotrophic factor and induce mesenchymal transition of oral tumor cells, Oral Oncol. 47 (2) (Feb. 2011) 98-103.
  12. J. Dudas, A. Fullar, M. Bitsche, V. Schartinger, I. Kovalszky, G.M. Sprinzl, H. Riechelmann, Tumor-produced, active Interleukin-1 beta regulates gene expression in carcinoma-associated fibroblasts, Exp. Cell Res. 317 (15) (Sep. 10 2011) 2222-2229.
  13. D. Docheva, D. Padula, C. Popov, P. Weishaupt, M. Pragert, N. Miosge, R. Hickel, W. Bocker, H. Clausen-Schaumann, M. Schieker, Establishment of immortalized periodontal ligament progenitor cell line and its behavioural analysis on smooth and rough titanium surface, Eur. Cell. Mater. 19 (2010) 228-241.
  14. K. Miyazawa, A. Mori, H. Okudaira, Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by glucocorticoids, J. Biochem. 124 (1998) 1130-1137.
  15. C.M. Yang, S.F. Luo, H.L. Hsieh, P.L. Chi, C.C. Lin, C.C. Wu, L.D. Hsiao, Interleukin-1beta induces ICAM-1 expression enhancing leukocyte adhesion in human rheumatoid arthritis synovial fibroblasts: involvement of ERK, JNK, AP-1, and NF-kappaB, J. Cell. Physiol. 224 (2010) 516-526.
  16. J. Dudas, T. Mansuroglu, F. Moriconi, F. Haller, J. Wilting, T. Lorf, L. Fuzesi, G. Ramadori, Altered regulation of Prox1-gene-expression in liver tumors, BMC Cancer 8 (2008) 92.
  17. F. Haller, B. Kulle, S. Schwager, B. Gunawan, A. von Heydebreck, H. Sultmann, L. Fuzesi, Equivalence test in quantitative reverse transcription polymerase chain reaction: confirmation of reference genes suitable for normalization, Anal. Biochem. 335 (2004) 1-9.
  18. S.F. Elliott, C.I. Coon, E. Hays, T.A. Stadheim, M.P. Vincenti, Bcl-3 is an interleukin-1-responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene, Arthritis Rheum. 46 (2002) 3230-3239.
  19. A. Moran, P. Iniesta, C. de Juan, R. Gonzalez-Quevedo, A. Sanchez-Pernaute, E. Diaz-Rubio, S. Cajal, A. Torres, J.L. Balibrea, M. Benito, Stromelysin-1 promoter mutations impair gelatinase B activation in high microsatellite instability sporadic colorectal tumors, Cancer Res. 62 (2002) 3855-3860.
  20. H. Sasaki, H. Yukiue, S. Moiriyama, Y. Kobayashi, Y. Nakashima, M. Kaji, M. Kiriyama, I. Fukai, Y. Yamakawa, Y. Fujii, Clinical significance of matrix metalloproteinase-7 and Ets-1 gene expression in patients with lung cancer, J. Surg. Res. 101 (2001) 242-247.
  21. M. Ueda, Y. Yamashita, M. Takehara, Y. Terai, K. Kumagai, K. Ueki, K. Kanda, Y.C. Hung, M. Ueki, Gene expression of adhesion molecules and matrix metalloproteinases in endometriosis, Gynecol. Endocrinol. 16 (2002) 391-402.
  22. S. Winter, A. Kohl, A. Huppertz, C. Herold-Mende, T. Wiest, G. Komposch, P. Tomakidi, Expression of mRNAs encoding for growth factors, ECM molecules, and MMP13 in mono-cultures and co-cultures of human periodontal ligament fibroblasts and alveolar bone cells, Cell Tissue Res. 319 (2005) 467-478.
  23. K. Sasaki, M. Takagi, J. Mandelin, I. Takei, S. Santavirta, H. Ida, T. Ogino, Y.T. Konttinen, Quantitative analysis of mRNA expression of TIMPs in the periprosthetic interface tissue of loose hips by real-time PCR system, J. Biomed. Mater. Res. 58 (2001) 605-612.
  24. Y. Yanai, M.J. Micallef, S. Yamamoto, K. Yamamoto, H. Yamauchi, H. Ikegami, M. Kurimoto, Expression profiling of tumor necrosis factor alpha-induced apoptosis-associated genes in human solid tumor cell lines, Anticancer Res. 23 (2003) 2339-2348.
  25. C.D. Hough, K.R. Cho, A.B. Zonderman, D.R. Schwartz, P.J. Morin, Coordinately up-regulated genes in ovarian cancer, Cancer Res. 61 (2001) 3869-3876.
  26. M. Wenghoefer, A. Pantelis, T. Najafi, J. Deschner, J.P. Allam, N. Novak, R. Reich, M. Martini, S. Berge, H.P. Fischer, S. Jepsen, J. Winter, Gene expression of oncogenes, antimicrobial peptides, and cytokines in the development of oral leukoplakia, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 110 (2010) 351-356.
  27. A.T. Rogojina, W.E. Orr, B.K. Song, E.E. Geisert Jr., Comparing the use of Affymetrix to spotted oligonucleotide microarrays using two retinal pigment epithelium cell lines, Mol. Vis. 9 (2003) 482-496.
  28. J. Dudas, G. Ramadori, T. Knittel, K. Neubauer, D. Raddatz, K. Egedy, I. Kovalszky, Effect of heparin and liver heparan sulphate on interaction of HepG2-derived transcription factors and their cis-acting elements: altered potential of hepatocellular carcinoma heparan sulphate, Biochem. J. 350 (Pt 1) (2000) 245-251.
  29. W.K. Tse, D.W. Au, C.K. Wong, Characterization of ion channel and transporter mRNA expressions in isolated gill chloride and pavement cells of seawater acclimating eels, Biochem. Biophys. Res. Commun. 346 (2006) 1181-1190.
  30. U.K. Laemmli, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227 (1970) 680-685.
  31. K. Baghy, K. Dezso, V. Laszlo, A. Fullar, B. Peterfia, S. Paku, P. Nagy, Z. Schaff, R.V. Iozzo, I. Kovalszky, Ablation of the decorin gene enhances experimental hepatic fibrosis and impairs hepatic healing in mice, Lab. Invest. 91 (2011) 439-451.
  32. G.T. Thomas, M.P. Lewis, P.M. Speight, Matrix metalloproteinases and oral cancer, Oral Oncol. 35 (1999) 227-233.
  33. G. Ge, D.S. Greenspan, BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein, J. Cell Biol. 175 (2006) 111-120.
  34. Y. Tokumaru, M. Fujii, Y. Otani, K. Kameyama, Y. Imanishi, N. Igarashi, J. Kanzaki, Activation of matrix metalloproteinase-2 in head and neck squamous cell carcinoma: studies of clinical samples and in vitro cell lines co-cultured with fibroblasts, Cancer Lett. 150 (2000) 15-21.
  35. J. Kusukawa, Y. Sasaguri, I. Shima, T. Kameyama, M. Morimatsu, Expression of matrix metalloproteinase-2 related to lymph node metastasis of oral squamous cell carcinoma. A clinicopathologic study, Am. J. Clin. Pathol. 99 (1993) 18-23.
  36. Y. Imanishi, M. Fujii, Y. Tokumaru, T. Tomita, M. Kanke, J. Kanzaki, K. Kameyama, Y. Otani, H. Sato, Clinical significance of expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 in human head and neck squamous cell carcinoma, Hum. Pathol. 31 (2000) 895-904.
  37. J.C. de Vicente, M.F. Fresno, L. Villalain, J.A. Vega, V.G. Hernandez, Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma, Oral Oncol. 41 (2005) 283-293.
  38. E.I. Deryugina, J.P. Quigley, Matrix metalloproteinases and tumor metastasis, Cancer Metastasis Rev. 25 (2006) 9-34.
  39. S.C. Lin, S.S. Lo, C.J. Liu, M.Y. Chung, J.W. Huang, K.W. Chang, Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for oral carcinogenesis, J. Oral Pathol. Med. 33 (2004) 405-409.
  40. S. Ishikawa, K. Takenaka, K. Yanagihara, R. Miyahara, Y. Kawano, Y. Otake, S. Hasegawa, H. Wada, F. Tanaka, Matrix metalloproteinase-2 status in stromal fibroblasts, not in tumor cells, is a significant prognostic factor in non-small-cell lung cancer, Clin. Cancer Res. 10 (2004) 6579-6585.
  41. Y. Hayashido, K. Urabe, Y. Yoshioka, H. Kitano, T. Okamoto, T. Matsuya, Participation of fibroblasts in MMP-2 binding and activation on the surface of oral squamous cell carcinoma cells, Int. J. Oncol. 22 (2003) 657-662.
  42. Y. Yang, D. Dang, A. Atakilit, B. Schmidt, J. Regezi, X. Li, D. Eisele, D. Ellis, D.M. Ramos, Specific alpha v integrin receptors modulate K1735 murine melanoma cell behavior, Biochem. Biophys. Res. Commun. 308 (2003) 814-819.
  43. S.W. Lin, F.C. Ke, P.W. Hsiao, P.P. Lee, M.T. Lee, J.J. Hwang, Critical involvement of ILK in TGFbeta1-stimulated invasion/migration of human ovarian cancer cells is associated with urokinase plasminogen activator system, Exp. Cell Res. 313 (2007) 602-613.
  44. B. Desai, M.J. Rogers, M.A. Chellaiah, Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells, Mol. Cancer 6 (2007) 18.
  45. A.H. Baker, D.R. Edwards, G. Murphy, Metalloproteinase inhibitors: biological actions and therapeutic opportunities, J. Cell Sci. 115 (2002) 3719-3727.
  46. R. Visse, H. Nagase, Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry, Circ. Res. 92 (2003) 827-839.
  47. H. Nagase, Cell surface activation of progelatinase A (proMMP-2) and cell migration, Cell Res. 8 (1998) 179-186.