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Volume 163, Issue 5

induces an upregulation of molecular biomarkers podoplanin, Wilms’ tumour gene 1, osteopontin and inflammatory cytokines in human mesothelial cells Free

Abstract

is the most prevalent infection of the genital tract in women worldwide. has a tendency to cause persistent infection and induce a state of chronic inflammation, which has been reported to play a role in carcinogenesis. We report that persistent infection increases the expression of inflammatory tumour cytokines and upregulates molecular biomarkers such as podoplanin, Wilms’ tumour gene 1 and osteopontin in primary cultures of mesothelial cells (Mes1) and human mesothelioma cells (NCI). Infection experiments showed that Mes1 and NCI supported the growth of , and at an m.o.i. of 4, the inclusion-forming units/cell showed many intracellular inclusion bodies after 3 days of infection. However, after 7 days of incubation, increased proliferative and invasive activity was also observed in Mes1 cells, which was more evident after 14 days of incubation. ELISA analysis revealed an increase in vascular endothelial growth factor, IL-6, IL-8, and TNF-α release in Mes1 cells infected for a longer period (14 days). Finally, real-time PCR analysis revealed a strong induction of podoplanin, Wilms’ tumour gene 1 and osteopontin gene expression in infected Mes1 cells. The aim of the present study was to investigate the inflammatory response elicited by persistent infection and the role played by inflammation in cell proliferation, secretion of proinflammatory cytokines and molecular biomarkers of cancer. The results of this study suggest that increased molecular biomarkers of cancer by persistent inflammation from infection might support cellular transformation, thus increasing the risk of cancer.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cytokines , osteopontin , podoplanin and Wilms’ tumour gene 1
© 2017 The Authors
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2017-05-01
2024-04-20
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References

  1. Samaras V, Rafailidis PI, Mourtzoukou EG, Peppas G, Falagas ME. Chronic bacterial and parasitic infections and cancer: a review. J Infect Dev Ctries 2010; 4:267–281[PubMed]
     [Google Scholar]
  2. O'Driscoll M, Jeggo PA. The role of double-strand break repair - insights from human genetics. Nat Rev Genet 2006; 7:45–54 [View Article][PubMed]
     [Google Scholar]
  3. Pate MS, Hedges SR, Sibley DA, Russell MW, Hook EW et al. Urethral cytokine and immune responses in Chlamydia trachomatis-infected males. Infect Immun 2001; 69:7178–7181 [View Article][PubMed]
     [Google Scholar]
  4. Madeleine MM, Anttila T, Schwartz SM, Saikku P, Leinonen M et al. Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer 2007; 120:650–655 [View Article][PubMed]
     [Google Scholar]
  5. Stephens RS. The cellular paradigm of chlamydial pathogenesis. Trends Microbiol 2003; 11:44–51 [View Article][PubMed]
     [Google Scholar]
  6. Chumduri C, Gurumurthy RK, Zadora PK, Mi Y, Meyer TF. Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe 2013; 13:746–758 [View Article][PubMed]
     [Google Scholar]
  7. Gurumurthy RK, Mäurer AP, Machuy N, Hess S, Pleissner KP et al. A loss-of-function screen reveals Ras- and Raf-independent MEK-ERK signaling during Chlamydia trachomatis infection. Sci Signal 2010; 3:ra21 [View Article][PubMed]
     [Google Scholar]
  8. Abdul-Sater AA, Saïd-Sadier N, Lam VM, Singh B, Pettengill MA et al. Enhancement of reactive oxygen species production and chlamydial infection by the mitochondrial Nod-like family member NLRX1. J Biol Chem 2010; 285:41637–41645 [View Article][PubMed]
     [Google Scholar]
  9. Hamon MA, Cossart P. Histone modifications and chromatin remodeling during bacterial infections. Cell Host Microbe 2008; 4:100–109 [View Article][PubMed]
     [Google Scholar]
  10. Schmeck B, Beermann W, N'Guessan PD, Hocke AC, Opitz B et al. Simvastatin reduces Chlamydophila pneumoniae-mediated histone modifications and gene expression in cultured human endothelial cells. Circ Res 2008; 102:888–895 [View Article][PubMed]
     [Google Scholar]
  11. Goering RV. Sexually transmitted diseases. In Goering R, Dockrell H, Roitt I, Zuckerman M, Wakelin D. (editors) Mims’ Medical Microbiology, 1st ed. Elsevier Limited; 2008 pp. 261–285 [CrossRef]
     [Google Scholar]
  12. Eckmann L, Kagnoff MF, Fierer J. Intestinal epithelial cells as watchdogs for the natural immune system. Trends Microbiol 1995; 3:118–120 [View Article][PubMed]
     [Google Scholar]
  13. Mao L, Hong WK. Focus on head and neck cancer. Cancer Cell 2004; 5:311–316 [View Article][PubMed]
     [Google Scholar]
  14. Hoshino A, Ishii G, Ito T, Aoyagi K, Ohtaki Y et al. Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation: podoplanin in fibroblast functions for tumor progression. Cancer Res 2011; 71:4769–4779 [View Article][PubMed]
     [Google Scholar]
  15. Schoppmann SF, Berghoff A, Dinhof C, Jakesz R, Gnant M et al. Podoplanin-expressing cancer-associated fibroblasts are associated with poor prognosis in invasive breast cancer. Breast Cancer Res Treat 2012; 134:237–244 [View Article][PubMed]
     [Google Scholar]
  16. Wai PY, Kuo PC. Osteopontin: regulation in tumor metastasis. Cancer Metastasis Rev 2008; 27:103–118 [View Article][PubMed]
     [Google Scholar]
  17. Weber GF, Lett GS, Haubein NC. Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer 2010; 103:861–869 [View Article][PubMed]
     [Google Scholar]
  18. Weber GF, Lett GS, Haubein NC. Meta-analysis of osteopontin as a clinical cancer marker. Oncol Rep 2011; 25:433–441 [View Article][PubMed]
     [Google Scholar]
  19. Weber GF, Zawaideh S, Kumar VA, Cantor H, Ashkar SJ. Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation. Leukoc Biol 2002; 72:752–761
     [Google Scholar]
  20. Jain S, Chakraborty G, Bulbule A, Kaur R, Kundu GC. Osteopontin: an emerging therapeutic target for anticancer therapy. Expert Opin Ther Targets 2007; 11:81–90 [View Article][PubMed]
     [Google Scholar]
  21. Scharnhorst V, van der Eb AJ, Jochemsen AG. WT1 proteins: functions in growth and differentiation. Gene 2001; 273:141–161 [View Article][PubMed]
     [Google Scholar]
  22. Nakatsuka S, Oji Y, Horiuchi T, Kanda T, Kitagawa M et al. Immunohistochemical detection of WT1 protein in a variety of cancer cells. Mod Pathol 2006; 19:804–814 [View Article][PubMed]
     [Google Scholar]
  23. Al-Salam S, Hammad FT, Salman MA, Alashari M. Expression of Wilms tumor-1 protein and CD 138 in malignant mesothelioma of the tunica vaginalis. Pathol Res Pract 2009; 205:797–800 [View Article][PubMed]
     [Google Scholar]
  24. Inoue K, Ogawa H, Yamagami T, Soma T, Tani Y et al. Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels. Blood 1996; 88:2267–2278[PubMed]
     [Google Scholar]
  25. Buommino E, Paoletti I, de Filippis A, Nicoletti R, Ciavatta ML et al. 3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells. Cell Prolif 2010; 43:114–123 [View Article][PubMed]
     [Google Scholar]
  26. Szczepulska-Wójcik E, Langfort R, Roszkowski-Sliz K. [A comparative evaluation of immunohistochemical markers for the differential diagnosis between malignant mesothelioma, non-small cell carcinoma involving the pleura, and benign reactive mesothelial cell proliferation]. Pneumonol Alergol Pol 2007; 75:57–69[PubMed]
     [Google Scholar]
  27. Rizzo A, Fiorentino M, Buommino E, Donnarumma G, Losacco A et al. Lactobacillus crispatus mediates anti-inflammatory cytokine interleukin-10 induction in response to Chlamydia trachomatis infection in vitro. Int J Med Microbiol 2015; 305:815–827 [View Article][PubMed]
     [Google Scholar]
  28. Rizzo A, Carratelli CR, Losacco A, Iovene MR. Antimicrobial effect of natural polyphenols with or without antibiotics on Chlamydia pneumoniae infection in vitro. Microb Drug Resist 2014; 20:1–10 [View Article][PubMed]
     [Google Scholar]
  29. Boonyanugomol W, Chomvarin C, Baik SC, Song JY, Hahnvajanawong C et al. Role of cagA-positive Helicobacter pylori on cell proliferation, apoptosis, and inflammation in biliary cells. Dig Dis Sci 2011; 56:1682–1692 [View Article][PubMed]
     [Google Scholar]
  30. Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res 1987; 47:3239–3245[PubMed]
     [Google Scholar]
  31. Huang W, Carlsen B, Rudkin G, Berry M, Ishida K et al. Osteopontin is a negative regulator of proliferation and differentiation in MC3T3-E1 pre-osteoblastic cells. Bone 2004; 34:799–808 [View Article][PubMed]
     [Google Scholar]
  32. Amin KM, Litzky LA, Smythe WR, Mooney AM, Morris JM et al. Wilms' tumor 1 susceptibility (WT1) gene products are selectively expressed in malignant mesothelioma. Am J Pathol 1995; 146:2[PubMed]
     [Google Scholar]
  33. Sawa Y, Iwasawa K, Ishikawa H. Expression of podoplanin in the mouse tooth germ and apical bud cells. Acta Histochem Cytochem 2008; 41:121–126 [View Article][PubMed]
     [Google Scholar]
  34. Knowlton AE, Fowler LJ, Patel RK, Wallet SM, Grieshaber SS. Chlamydia induces anchorage independence in 3t3 cells and detrimental cytological defects in an infection model. PLoS One 2013; 8:54022 [View Article]
     [Google Scholar]
  35. Greene W, Xiao Y, Huang Y, Mcclarty G, Zhong G. Chlamydia-infected cells continue to undergo mitosis and resist induction of apoptosis. Infect Immun 2004; 72:451–460 [View Article][PubMed]
     [Google Scholar]
  36. Quirk JT, Kupinski JM. Chronic infection, inflammation, and epithelial ovarian cancer. Med Hypotheses 2001; 57:426–428 [View Article][PubMed]
     [Google Scholar]
  37. Sellami H, Said-Sadier N, Znazen A, Gdoura R, Ojcius DM et al. Chlamydia trachomatis infection increases the expression of inflammatory tumorigenic cytokines and chemokines as well as components of the Toll-like receptor and NF-κB pathways in human prostate epithelial cells. Mol Cell Probes 2014; 28:147–154 [View Article][PubMed]
     [Google Scholar]
  38. Koskela P, Anttila T, Bjørge T, Brunsvig A, Dillner J et al. Chlamydia trachomatis infection as a risk factor for invasive cervical Cancer. Int J Cancer 2000; 85:35–39 [View Article][PubMed]
     [Google Scholar]
  39. Guo Y, Wang S, Hoot DR, Clinton SK. Suppression of VEGF-mediated autocrine and paracrine interactions between prostate cancer cells and vascular endothelial cells by soy isoflavones. J Nutr Biochem 2007; 18:408–417 [View Article][PubMed]
     [Google Scholar]
  40. Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC et al. Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology 1998; 51:161–167 [View Article][PubMed]
     [Google Scholar]
  41. Lu H, Ouyang W, Inflammation HC. A key event in cancer development. Mol Cancer Res 2006; 4:221–233 [CrossRef]
     [Google Scholar]
  42. Di JM, Pang J, Pu XY, Zhang Y, Liu XP et al. Toll-like receptor 9 agonists promote IL-8 and TGF-beta1 production via activation of nuclear factor kappaB in PC-3 cells. Cancer Genet Cytogenet 2009; 192:60–67 [View Article][PubMed]
     [Google Scholar]
  43. Drott JB, Alexeyev O, Bergström P, Elgh F, Olsson J. Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells. BMC Microbiol 2010; 10:126 [View Article][PubMed]
     [Google Scholar]
  44. Takeyama K, Mitsuzawa H, Shimizu T, Konishi M, Nishitani C et al. Prostate cell lines secrete IL-8 in response to Mycoplasma hominis through Toll-like receptor 2-mediated mechanism. Prostate 2006; 66:386–391 [View Article][PubMed]
     [Google Scholar]
  45. Burke F, Relf M, Negus R, Balkwill F. A cytokine profile of normal and malignant ovary. Cytokine 1996; 8:578–585 [View Article][PubMed]
     [Google Scholar]
  46. Wicki A, Christofori G. The potential role of podoplanin in tumour invasion. Br J Cancer 2007; 96:1–5 [View Article][PubMed]
     [Google Scholar]
  47. Bartuli FN, Luciani F, Caddeo F, Compagni S, Piva P et al. Podoplanin in the development and progression of oral cavity cancer: a preliminary study. Oral Implantol 2012; 5:33–41[PubMed]
     [Google Scholar]
  48. Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev 2008; 19:333–345 [View Article][PubMed]
     [Google Scholar]
  49. Hartung F, Weber GF. RNA blood levels of osteopontin splice variants are cancer markers. Springerplus 2013; 2:110 [View Article][PubMed]
     [Google Scholar]
  50. Guo H, Cai CQ, Schroeder RA, Kuo PC. Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages. J Immunol 2001; 166:1079–1086 [View Article][PubMed]
     [Google Scholar]
  51. Denhardt DT, Noda M, O'Regan AW, Pavlin D, Berman JS. Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest 2001; 107:1055–1061 [View Article][PubMed]
     [Google Scholar]
  52. Zhao J, Dong L, Lu B, Wu G, Xu D et al. Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis. Gastroenterology 2008; 135:956–968 [View Article][PubMed]
     [Google Scholar]
  53. Blasberg JD, Pass HI, Goparaju CM, Flores RM, Lee S et al. Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 2010; 28:936–941 [View Article][PubMed]
     [Google Scholar]
  54. Lund SA, Giachelli CM, Scatena M. The role of osteopontin in inflammatory processes. J Cell Commun Signal 2009; 3:311–322 [View Article][PubMed]
     [Google Scholar]
  55. Yang L, Han Y, Suarez Saiz F, Minden MD. A tumor suppressor and oncogene: the WT1 story. Leukemia 2007; 21:868–876 [View Article][PubMed]
     [Google Scholar]
  56. Oji Y, Inohara H, Nakazawa M, Nakano Y, Akahani S et al. Overexpression of the Wilms' tumor gene WT1 in head and neck squamous cell carcinoma. Cancer Sci 2003; 94:523–529 [View Article][PubMed]
     [Google Scholar]
  57. Langman G, Andrews CL, Weissferdt A. WT1 expression in salivary gland pleomorphic adenomas: a reliable marker of the neoplastic myoepithelium. Mod Pathol 2011; 24:168–174 [View Article][PubMed]
     [Google Scholar]
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Chlamydia trachomatis induces an upregulation of molecular biomarkers podoplanin, Wilms’ tumour gene 1, osteopontin and inflammatory cytokines in human mesothelial cells
Microbiology 163, 654 (2017); https://doi.org/10.1099/mic.0.000465
/content/journal/micro/10.1099/mic.0.000465
/content/journal/micro/10.1099/mic.0.000465
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