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Published in: Tumor Biology 4/2012

01-08-2012 | Research Article

Poly(I:C) treatment influences the expression of calreticulin and profilin-1 in a human HNSCC cell line: a proteomic study

Authors: Tanja Matijević, Jasminka Pavelić

Published in: Tumor Biology | Issue 4/2012

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Abstract

Polyinosinic:polycytidylic acid (poly (I:C)) has been formerly known to be an interferon inducer but the mechanism of its action was not revealed until the discovery of Toll-like receptors (TLRs). TLRs are members of transmembrane proteins that recognize conserved molecular motifs of viral and bacterial origin and initiate innate immune response. Recent studies have shown that they are also expressed on tumor cells, but their role in these cells is still not clear. TLR3 recognizes double-stranded RNA (poly (I:C)) and is primarily involved in the defense against viruses. TLR3 ligand binding initiates the activation of transcription factors NF-κB, IRF family members, and AP-1, which can induce wide cascading effect on the cell and consequently activate many cellular processes. Since little is known about TLR3 target genes, we have used the proteomic approach to widen the current knowledge. In this study, we have discovered 15 differentially expressed proteins, mostly connected with protein metabolic processes. Furthermore, we have confirmed by Western blot that calreticulin and profilin-1, proteins which have been shown previously to be involved in processes connected with tumor progression, are differentially expressed after poly(I:C) treatment. By using TLR3 small interfering RNA, we showed that calreticulin expression might be TLR3 dependent, unlike profilin-1.
Literature
1.
go back to reference Medzhitov R, Preston-Hurlburt P, Janeway Jr CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388:394–7.CrossRef Medzhitov R, Preston-Hurlburt P, Janeway Jr CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388:394–7.CrossRef
2.
go back to reference Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A. 1998;95:588–93.CrossRef Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A. 1998;95:588–93.CrossRef
3.
go back to reference Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T. TLR3 can directly trigger apoptosis in human cancer cells. J Immunol. 2006;176:4894–901.CrossRef Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T. TLR3 can directly trigger apoptosis in human cancer cells. J Immunol. 2006;176:4894–901.CrossRef
4.
go back to reference Salaun B, Lebecque S, Matikainen S, Rimoldi D, Romero P. Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res. 2007;13:4565–74.CrossRef Salaun B, Lebecque S, Matikainen S, Rimoldi D, Romero P. Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res. 2007;13:4565–74.CrossRef
5.
go back to reference Khvalevsky E, Rivkin L, Rachmilewitz J, Galun E, Giladi H. TLR3 signaling in a hepatoma cell line is skewed towards apoptosis. J Cell Biochem. 2007;100:1301–12.CrossRef Khvalevsky E, Rivkin L, Rachmilewitz J, Galun E, Giladi H. TLR3 signaling in a hepatoma cell line is skewed towards apoptosis. J Cell Biochem. 2007;100:1301–12.CrossRef
6.
go back to reference Paone A, Galli R, Gabellini C, Lukashev D, Starace D, Gorlach A, et al. Toll-like receptor 3 regulates angiogenesis and apoptosis in prostate cancer cell lines through hypoxia-inducible factor 1 alpha. Neoplasia. 2010;12:539–49.CrossRef Paone A, Galli R, Gabellini C, Lukashev D, Starace D, Gorlach A, et al. Toll-like receptor 3 regulates angiogenesis and apoptosis in prostate cancer cell lines through hypoxia-inducible factor 1 alpha. Neoplasia. 2010;12:539–49.CrossRef
7.
go back to reference McCall KD, Harii N, Lewis CJ, Malgor R, Kim WB, Saji M, et al. High basal levels of functional toll-like receptor 3 (TLR3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazole together with cell proliferation and migration. Endocrinology. 2007;148:4226–37.CrossRef McCall KD, Harii N, Lewis CJ, Malgor R, Kim WB, Saji M, et al. High basal levels of functional toll-like receptor 3 (TLR3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazole together with cell proliferation and migration. Endocrinology. 2007;148:4226–37.CrossRef
8.
go back to reference Schwartz AL, Malgor R, Dickerson E, Weeraratna AT, Slominski A, Wortsman J, et al. Phenylmethimazole decreases Toll-like receptor 3 and noncanonical Wnt5a expression in pancreatic cancer and melanoma together with tumor cell growth and migration. Clin Cancer Res. 2009;15:4114–22.CrossRef Schwartz AL, Malgor R, Dickerson E, Weeraratna AT, Slominski A, Wortsman J, et al. Phenylmethimazole decreases Toll-like receptor 3 and noncanonical Wnt5a expression in pancreatic cancer and melanoma together with tumor cell growth and migration. Clin Cancer Res. 2009;15:4114–22.CrossRef
9.
go back to reference Jasani B, Navabi H, Adams M. Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine. 2009;27:3401–4.CrossRef Jasani B, Navabi H, Adams M. Ampligen: a potential toll-like 3 receptor adjuvant for immunotherapy of cancer. Vaccine. 2009;27:3401–4.CrossRef
10.
go back to reference Kopp EB, Medzhitov R. The Toll-receptor family and control of innate immunity. Curr Opin Immunol. 1999;11:13–8.CrossRef Kopp EB, Medzhitov R. The Toll-receptor family and control of innate immunity. Curr Opin Immunol. 1999;11:13–8.CrossRef
11.
go back to reference Zhang FX, Kirschning CJ, Mancinelli R, Xu XP, Jin Y, Faure E, et al. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem. 1999;274:7611–4.CrossRef Zhang FX, Kirschning CJ, Mancinelli R, Xu XP, Jin Y, Faure E, et al. Bacterial lipopolysaccharide activates nuclear factor-kappaB through interleukin-1 signaling mediators in cultured human dermal endothelial cells and mononuclear phagocytes. J Biol Chem. 1999;274:7611–4.CrossRef
12.
go back to reference Navarro L, David M. p38-Dependent activation of interferon regulatory factor 3 by lipopolysaccharide. J Biol Chem. 1999;274:35535–8.CrossRef Navarro L, David M. p38-Dependent activation of interferon regulatory factor 3 by lipopolysaccharide. J Biol Chem. 1999;274:35535–8.CrossRef
13.
go back to reference Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999;18:6853–66.CrossRef Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999;18:6853–66.CrossRef
14.
go back to reference Hartl M, Bader AG, Bister K. Molecular targets of the oncogenic transcription factor jun. Curr Cancer Drug Targets. 2003;3:41–55.CrossRef Hartl M, Bader AG, Bister K. Molecular targets of the oncogenic transcription factor jun. Curr Cancer Drug Targets. 2003;3:41–55.CrossRef
15.
go back to reference Rakkola R, Matikainen S, Nyman TA. Proteome analysis of human macrophages reveals the upregulation of manganese-containing superoxide dismutase after Toll-like receptor activation. Proteomics. 2007;7:378–84.CrossRef Rakkola R, Matikainen S, Nyman TA. Proteome analysis of human macrophages reveals the upregulation of manganese-containing superoxide dismutase after Toll-like receptor activation. Proteomics. 2007;7:378–84.CrossRef
16.
go back to reference Haglund L, Bernier SM, Onnerfjord P, Recklies AD. Proteomic analysis of the LPS-induced stress response in rat chondrocytes reveals induction of innate immune response components in articular cartilage. Matrix Biol. 2008;27:107–18.CrossRef Haglund L, Bernier SM, Onnerfjord P, Recklies AD. Proteomic analysis of the LPS-induced stress response in rat chondrocytes reveals induction of innate immune response components in articular cartilage. Matrix Biol. 2008;27:107–18.CrossRef
17.
go back to reference Madan M, Amar S. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings. PLoS One. 2008;3:e3204.CrossRef Madan M, Amar S. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings. PLoS One. 2008;3:e3204.CrossRef
18.
go back to reference Wang T, Gu S, Ronni T, Du YC, Chen X. In vivo dual-tagging proteomic approach in studying signaling pathways in immune response. J Proteome Res. 2005;4:941–9.CrossRef Wang T, Gu S, Ronni T, Du YC, Chen X. In vivo dual-tagging proteomic approach in studying signaling pathways in immune response. J Proteome Res. 2005;4:941–9.CrossRef
19.
go back to reference Matijevic T, Marjanovic M, Pavelic J. Functionally active Toll-like receptor 3 on human primary and metastatic cancer cells. Scand J Immunol. 2009;70:18–24.CrossRef Matijevic T, Marjanovic M, Pavelic J. Functionally active Toll-like receptor 3 on human primary and metastatic cancer cells. Scand J Immunol. 2009;70:18–24.CrossRef
20.
go back to reference Matijevic T, Pavelic J. (2011) The dual role of TLR3 in metastatic cell line. Clin Exp Metastasis. 2011;28:701–12.CrossRef Matijevic T, Pavelic J. (2011) The dual role of TLR3 in metastatic cell line. Clin Exp Metastasis. 2011;28:701–12.CrossRef
21.
go back to reference Shevchenko A, Wilm M, Vorm O, Mann M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 1996;68:850–8.CrossRef Shevchenko A, Wilm M, Vorm O, Mann M. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 1996;68:850–8.CrossRef
22.
go back to reference Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A, Saavedra E. Energy metabolism in tumor cells. FEBS J. 2007;274:1393–418.CrossRef Moreno-Sanchez R, Rodriguez-Enriquez S, Marin-Hernandez A, Saavedra E. Energy metabolism in tumor cells. FEBS J. 2007;274:1393–418.CrossRef
23.
go back to reference Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452:230–3.CrossRef Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature. 2008;452:230–3.CrossRef
24.
go back to reference Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P. Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta. 2010;1805:53–71.PubMed Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P. Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta. 2010;1805:53–71.PubMed
25.
go back to reference Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, et al. Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med. 1998;188:2349–56.CrossRef Pike SE, Yao L, Jones KD, Cherney B, Appella E, Sakaguchi K, et al. Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth. J Exp Med. 1998;188:2349–56.CrossRef
26.
go back to reference Pike SE, Yao L, Setsuda J, Jones KD, Cherney B, Appella E, et al. Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth. Blood. 1999;94:2461–8.CrossRef Pike SE, Yao L, Setsuda J, Jones KD, Cherney B, Appella E, et al. Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth. Blood. 1999;94:2461–8.CrossRef
27.
go back to reference Das T, Bae YH, Wells A, Roy P. Profilin-1 overexpression upregulates PTEN and suppresses AKT activation in breast cancer cells. J Cell Physiol. 2009;218:436–43.CrossRef Das T, Bae YH, Wells A, Roy P. Profilin-1 overexpression upregulates PTEN and suppresses AKT activation in breast cancer cells. J Cell Physiol. 2009;218:436–43.CrossRef
28.
go back to reference Zou L, Ding Z, Roy P. Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation. J Cell Physiol. 2010;223:623–9.PubMedPubMedCentral Zou L, Ding Z, Roy P. Profilin-1 overexpression inhibits proliferation of MDA-MB-231 breast cancer cells partly through p27kip1 upregulation. J Cell Physiol. 2010;223:623–9.PubMedPubMedCentral
29.
go back to reference Zou L, Jaramillo M, Whaley D, Wells A, Panchapakesa V, Das T, et al. Profilin-1 is a negative regulator of mammary carcinoma aggressiveness. Br J Cancer. 2007;97:1361–71.CrossRef Zou L, Jaramillo M, Whaley D, Wells A, Panchapakesa V, Das T, et al. Profilin-1 is a negative regulator of mammary carcinoma aggressiveness. Br J Cancer. 2007;97:1361–71.CrossRef
30.
go back to reference Janke J, Schluter K, Jandrig B, Theile M, Kolble K, Arnold W, et al. Suppression of tumorigenicity in breast cancer cells by the microfilament protein profilin 1. J Exp Med. 2000;191:1675–86.CrossRef Janke J, Schluter K, Jandrig B, Theile M, Kolble K, Arnold W, et al. Suppression of tumorigenicity in breast cancer cells by the microfilament protein profilin 1. J Exp Med. 2000;191:1675–86.CrossRef
31.
go back to reference Minamida S, Iwamura M, Kodera Y, Kawashima Y, Ikeda M, Okusa H, et al. Profilin 1 overexpression in renal cell carcinoma. Int J Urol. 2011;18:63–71.CrossRef Minamida S, Iwamura M, Kodera Y, Kawashima Y, Ikeda M, Okusa H, et al. Profilin 1 overexpression in renal cell carcinoma. Int J Urol. 2011;18:63–71.CrossRef
32.
go back to reference Tanaka M, Sasaki H, Kino I, Sugimura T, Terada M. Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer. Cancer Res. 1992;52:3372–7.PubMed Tanaka M, Sasaki H, Kino I, Sugimura T, Terada M. Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer. Cancer Res. 1992;52:3372–7.PubMed
33.
go back to reference Huang CM, Ananthaswamy HN, Barnes S, Ma Y, Kawai M, Elmets CA. Mass spectrometric proteomics profiles of in vivo tumor secretomes: capillary ultrafiltration sampling of regressive tumor masses. Proteomics. 2006;6:6107–16.CrossRef Huang CM, Ananthaswamy HN, Barnes S, Ma Y, Kawai M, Elmets CA. Mass spectrometric proteomics profiles of in vivo tumor secretomes: capillary ultrafiltration sampling of regressive tumor masses. Proteomics. 2006;6:6107–16.CrossRef
34.
go back to reference Ding Z, Gau D, Deasy B, Wells A, Roy P. Both actin and polyproline interactions of profilin-1 are required for migration, invasion and capillary morphogenesis of vascular endothelial cells. Exp Cell Res. 2009;315:2963–73.CrossRef Ding Z, Gau D, Deasy B, Wells A, Roy P. Both actin and polyproline interactions of profilin-1 are required for migration, invasion and capillary morphogenesis of vascular endothelial cells. Exp Cell Res. 2009;315:2963–73.CrossRef
35.
go back to reference Sigoillot FD, King RW. Vigilance and validation: keys to success in RNAi screening. ACS Chem Biol. 2011;6:47–60.CrossRef Sigoillot FD, King RW. Vigilance and validation: keys to success in RNAi screening. ACS Chem Biol. 2011;6:47–60.CrossRef
36.
go back to reference Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNAs. Genes Dev. 2003;17:438–42.CrossRef Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNAs. Genes Dev. 2003;17:438–42.CrossRef
37.
go back to reference Jackson AL, Linsley PS. Noise amidst the silence: off-target effects of siRNAs? Trends Genet. 2004;20:521–4.CrossRef Jackson AL, Linsley PS. Noise amidst the silence: off-target effects of siRNAs? Trends Genet. 2004;20:521–4.CrossRef
38.
go back to reference Romeo GR, Kazlauskas A. Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. J Biol Chem. 2008;283:9595–605.CrossRef Romeo GR, Kazlauskas A. Oxysterol and diabetes activate STAT3 and control endothelial expression of profilin-1 via OSBP1. J Biol Chem. 2008;283:9595–605.CrossRef
39.
go back to reference Qiu Y, Michalak M. Transcriptional control of the calreticulin gene in health and disease. Int J Biochem Cell Biol. 2009;41:531–8.CrossRef Qiu Y, Michalak M. Transcriptional control of the calreticulin gene in health and disease. Int J Biochem Cell Biol. 2009;41:531–8.CrossRef
40.
go back to reference Cheng YS, Xu F. Anticancer function of polyinosinic–polycytidylic acid. Cancer Biol Ther. 2010;10:1219–23.CrossRef Cheng YS, Xu F. Anticancer function of polyinosinic–polycytidylic acid. Cancer Biol Ther. 2010;10:1219–23.CrossRef
Metadata
Title
Poly(I:C) treatment influences the expression of calreticulin and profilin-1 in a human HNSCC cell line: a proteomic study
Authors
Tanja Matijević
Jasminka Pavelić
Publication date
01-08-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0366-7

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