• Nenhum resultado encontrado

Com base nos resultados obtidos neste estudo, pode-se concluir que:

1. Os TAMs são capazes de secretar exossomos quando diferenciados em monócitos a partir de células THP1 e quando polarizados em macrófagos M1 e M2. Este achado foi confirmado pela presença de exossomos positivos para o marcador de superfície CD63;

2. Os exossomos derivados de TAMs M1 e das células THP1 apresentaram escassa marcação para TGF- . Não obstante os exossomos derivados dos macrófagos M2 apresentarem positividade para TGF- . No que concerne ao exossomos derivados das linhagens celulares SCC-25, SAS e HSC-3, não foi possível observar a presença de marcação para esta proteína, sugerindo que os exossomos das células de CE de língua não apresentam TGF- em seu interior;

3. As células SCC-25 cultivadas juntamente com os exossomos, no ensaio de invasão utilizando o meio de cultura DMEM F/12, apresentaram maior tendência de invasão através do miogel para a concentração 10 µg/ml dos exossomos derivados de M2. A linhagem celular HSC-3 apresentou menor capacidade invasiva em meio DMEM F/12. No meio de cultura com ausência de FBS, percebeu-se que houve uma maior capacidade invasiva pelas células HSC-3, de forma quantitativa, apesar da ausência de relação estatisticamente significativa. A linhagem de células SAS não apresentou maior capacidade invasiva quando comparados os diferentes meios de cultura;

4. Quanto à capacidade de atração das linhagens celulares pelos exossomos, foi possível inferir que a linhagem celular SCC-25 não apresentou maior capacidade de invasão quando os exossomos estavam localizados no compartimento inferior do transwell. Ao passo que a linhagem HSC-3 apresentou maior capacidade de invadir quando em presença dos exossomos M2 (1,0 µg/ml) no compartimento inferior do transwell;

5. Os ensaios de proliferação e viabilidade celular utilizando a linhagem HSC-3 apresentaram discreto aumento na viabilidade celular em presença de exossomos M2 (1,0 µg/ml) em meio de cultura DMEM F/12. A linhagem celular SCC-25 apresentou aumento na proliferação em presença de exossomos M2 (50 µg/ml) para ambos os meios de culturas estudados;

6. O estudo da imunofluorescência possibilitou a observação de que exossomos derivados de TAMs apresentam capacidade de internalização nas células de CE de língua.

REFERÊNCIAS

AKDIS, C.A.; BLASER, K. IL-10 induced energy in peripheral T cell and reactivation by microenvironmental cytokines: two key steps in specific immunotherapy. FASEB J., v. 103, n. 2, p. 603-9, 1999.

AKERS, J.C., et al. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neuro oncol. v.113, n.1, p.1-11, 2013.

ALLAVENA, P. IL-10 prevents the differentiation of monocytes to dentritic cells but promotes maturation to pacrophages. Eur. J. Immunol. v.28, n.1, p.359–69, 1998.

ALLAVENA, P. et al. The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit. Rev. Oncol. Hematol. v.66, n.1, p.1-9, 2008.

ALMAGUSH, A. Depth of invasion, tumor budding, and worst pattern of invasion: Prognostic indicators in early-stage oral tongue cancer. Head and neck. v.36, n.6, p.811-8, 2014.

ANDRE, F. et al. Exosomes for cancer immunotherapy. Ann Oncol, v. 15, p. 141-4, 2004. ANNES J.P., MUNGER J.S., RIFKIN D.B. Making sense of latent TGF-beta activation. J. Cell Sci. v.116, n.2, p.217-24, 2003.

B.J. Quah, H.C. O'Neill, The immunogenicity of dendritic cell derived exosomes. Blood cells Mol. Dis. v.35, n.2, p.94-110, 2005.

BENITO-MARTIN, A. et al. The new deal: a potential role for secreted vesicles in innate immunity and tumor progression. Frontiersin., v. 6, n.66, p. 1-13, 2015.

BISWAS, S.K.; SICA, A.; LEWIS, C.E. Plasticity of macrophage function during tumor progression: regulation by distinct molecular mechanisms. J. Immunol., v. 180, n.4 p. 2011-7, 2008.

BLOT, E. et al. Co-operation between monocytes and breast cancer cells promotes factors involved in cancer aggressiveness. Br. J. Cancer., v. 88, n.8, p. 1207-12, 2003.

BRENER, S. et al. Carcinoma de células escamosas bucal: uma revisão de literatura entre o perfil do paciente, estadiamento clínico e tratamento proposto. Res Biol Celular., v. 53, p. 63- 9, 2007.

CAI J. et al. BMP and TGF- pathway mediators are critical upstream regulators of Wnt signaling during midbrain dopamine differentiation in human pluripotent stem cells. Dev Biol. v.376, n.1, p.62-73, 2013.

CASWELL, P.T.; NORMAN, J.C. Integrin trafficking and the control of cell migration. Traffic, v. 7, n.1, p. 14-21, 2006.

CHAFFER, C. L. & WEINBERG, R. A perspective on cancer cell metastasis. Science v.331, n.1, p.1559– 1564, 2011.

CHATENOUD L. et al. Immune therapies of autoimmune diseases: are we approaching a real cure? Curr Opin Immunol. v.18, n.6, p.710-7, 2006.

CHATZISTAMOU, I. et al. Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongue. J Oral Pathol Med, v. 39, n.9, p. 667-71, 2010.

CHOW, A. et al. Macrophage immunomodulation by breast cancer-derived exosomes requires Toll-like receptor 2-mediated activation of NF-kB. Sci. Rep. v.18, n.4, p.1-11, 2014.

COCUCCI, E.; RACCHETTI, G.; MELDOLESI, J. Shedding microvesicles: artefacts no more. Trends Cell Biol., v. 19, n.2, p. 43-51, 2009.

COLOMBO, M.; RAPOSO, G.; THÉRY C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell. Dev. Biol. v.30, p.255-89, 2014. CONDEELIS, J.; POLLARD, J.W. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.Cell. v.124, n.2, p.263-6, 2006.

COSTA, A.L.L. et al. Correlação entre a classificação TNM, gradação histológica e localização anatômica em carcinoma epidermóide oral. Pesqui Odontol Bras., v. 16, n.3, p. 216-220, 2002. COSTA, N.L. Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma.Oral Oncol. v.49, n.3, p.216–223, 2013.

COSTA-SILVA, B. et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver Nat. Cell Biol. v.17, n.6, p.1-7, 2015.

DE TORO, J. et al. Emerging roles of exosomes in normal and pathological conditions: new insights for diagnosis and therapeutic applications. Frontiersin., v. 6, p. 1-12, 2015.

DEMORY B. M. Proteomic analysis of exosomes from mutant KRAS colon cancer cells identify intercellular transfer of mutant KRAS. MCP. DOI: 10.1074/mcp.M112.022806. DERYNCK, R.; AKHURST, R.J. Differentiation plasticity regulated by TGF-� family proteins in development and disease. Nature Cell Biology, v. 9, p. 1000-4, 2007.

DUNN, G. P., OLD, L.J.; SCHREIBER, R.D. The three Es of cancer immunoediting. Annu. Rev. Immunol. v. 22, p. 329-60, 2004.

DUNN, G.P. Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. v.3, n.11, p.991-8, 2002.

DUNN, G.P.; KOEBEL, C.M.; SCHREIBER, R.D. Interferons,immunity and cancer immu- noediting. Nat. Rev. Immunol., v. 6, n.11, p. 836-48, 2006.

DVORAK, H.F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med., v. 315, n.26, p. 1650-9, 1986.

FARAHANI, M. et al, (2015) CLL Exosomes Modulate the ranscriptome and Behaviour of Recipient Stromal Cells and Are Selectively Enriched in miR-202-3p. PLoS ONE v.10, n.10,p. e0141429, 2015. DOI:10.1371/journal.

FÉVRIER, B.; RAPOSO, G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Current Opinion in Cell Biology, v. 16, n.4, p. 415-21, 2004.

GAJEWSKI, T.F.; SCHREIBERH, H.; FU, Y.X. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol., v. 14, n.10, p. 1014-22, 2013.

GHABLY, J. et al. Paul Ehrlich’s Mastzellen: a historical perspective of relevant developments in mast cell biology. Methods Mol Biol v. 1220, p. 3-10, 2015.

GHOLAMIN M et al. Overexpression and Interactions of Interleukin-10, Transforming Growth Factor , and Vascular Endothelial Growth Factor in Esophageal Squamous Cell Carcinoma. World J. Surg. v.33, n.7, p.1439-1445, 2009.

GORDON, S. Alternative activation of macrophages. Nat. Rev. Immunol., v. 3, n.1, p. 23-35, 2003.

GORELIK E. et al. Herberman, Augmentation of metastasis formation by thioglycollate- elicited macrophages. Int. J. Cancer. v.29, n.5, p575–81, 1982.

GORELINK, L.; FLAVELL, R.A. Immune-mediated eradication of tumors through the blockade of transforming growth factor-� signaling in T cells. Nat. Medicine, vol. 7, n. 10, p. 1118-1122, 2001.

GREENING D.W. et al. Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. Semin. Cell Dev. Biol. v.40, p.60-71, 2015.

GUILLEM E.B., et al. Vascular endothelial growth factor secretion by tumor-infiltrating macrophages essentially supports tumor angiogenesis, and IgG immune complexes potentiate the process. Cancer Res. v.62, n.23, p.7042-9, 2002.

GUPTA, G.P.; MASSAGUE, J. Cancer metastasis: building a frame work. Cell, v. 127, n.4, p. 679-95, 2006.

GURUVAYOORAPPAN, C. Tumor Versus Tumor-Associated Macrophages: How Hot is the Link?. Integr. Cancer Ther., v. 7, n.2, p. 90, 2008.

HADDADIN, K.J. et al. Improved survival for patients with clinically T1 ⁄ Tβ, N0 tongue tumors undergoing a prophylactic neck dissection. Head Neck, v. 21, n.6, p. 517-25, 1999. HADLER-OLSEN, E. et al. Regulation of matrix metalloproteinase activity in health and disease. FEBS J., v. 278, n.1, p. 28-45, 2011.

HAGEMANN, T. et al. Regulation of macrophage function in tumors: the multifaceted role of NF-κB. Blood., v. 113, n.14, p. 3139-46, 2009.

HANAHAN, D.; WEINBERD, R.A. The hallmarks of cancer. Cell., v. 100, n.1, p. 57-70, 2000. HARSHYNE L. A. et al. Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients. Euro Oncol. 2015. [No prelo]

HEMLER, M.E. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol., v. 19, p. 397- 422, 2003.

HESSVIK, N.P. et al. Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells. Biochim. Biophys. Acta., v. 1819, n. 11-12, p. 1154-1163, 2012.

HIRANO, C. et al. Tetraspanin gene expression levels as potential biomarkers for malignancy of gingival squamous cell carcinoma. Int. J. Cancer., v. 124, n.12, p. 2911-16, 2009.

HONG, C.S. et al. Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Frontiersin., v. 5, v.160, p. 1-9, 2014.

HUNTER, M.P. et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One, v. 3, n. 11, p. 1-11, 2008.

HURLEY, J.H. The ESCRT complexes. Crit Rev. Biochem. Mol. Biol., v. 45, n.6, p. 463-48, 2010.

WYCKOFF, J.B. et al. Intravasation in Mammary Tumors Cancer Res. v.67, n.6, p.2649–56, 2007.

ISMAIL, N. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood, v. 121, n.6, p. 984-995, 2013.

JAKOBSEN K.R. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma. J. Extracell. Vesicles. v.4, n.26659, 2015. DOI: 10.3402/jev.v4.26659. JANG, J.Y. et al. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization. BMC Cancer., v. 17, n.13, p. 1-12, 2013.

JOHNSTONE, R.M. et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). Biol Chem. v.262, n.19, p.9412-20, 1987.

KAHLERT, C.; KALLURI, R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med, v. 91, n.4, p. 431-37, 2013.

KALANI A. et al. Curcumin-Primed Exosomes Mitigate Endothelial Cell Dysfunction during Hyperhomocysteinemia Life Sci. v.107, n.1-2, p.1-7, 2014.

KALLURI R, WEINBERG RA. The basics of epithelial mesenchymal transition. J. Clin. Invest. v.119, n.6, p.1420-8; 2009.

KALLURI, R.; ZEISBERG, M. Fibroblasts in cancer. Nat Rev Cancer, v. 6, n.5, p. 392-401, 2006.

KATAKI, A. et al. Tumor infiltrating lymphocytes and macrophages have a potential dual role in lung cancer by supporting both host-defense and tumor progression. J. Lab. Clin. Med. v.140, n.5, p.320-8, 2002.

KELLER, S. et al. Exosomes: from biogenesis and secretion to biological function. Immunol Lett., v. 107, n.2, p. 02-8, 2006.

KESKI-SANTTI, H. et al. Elective neck treatment versus observation in patients with T1 ⁄ Tβ N0 squamous cell carcinoma of oral tongue. Oral Oncol, v. 42, n.1, p. 96-101, 2006.

KIM J., et al. Enhanced shedding of extracellular vesicles from amoeboid prostate cancer cells Potential effects on the tumor microenvironment. Cancer Biol. Ther. v.15, n.4, p.409-18, 2014. KOIDE, N. et al. Significance of macrophage chemoattractant proteín-1 expression and macrophage infiltration in squamous cell carcinoma of the esophagus. Am. J. Gatroenterol. v.99, n.9, p. 1667-1674, 2004.

KUMAR, D. et al. Biomolecular characterization of exosomes released from cancer stem cells: possible implications for biomarker and treatment of cancer. Onco target., v. 6, n.5, p. 3280- 91, 2014.

LAMPARSKI, H.G. et al. Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods., v.15, n.270, p. 211-26, 2002.

LÄSSER, C. et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med, v. 14, n.9, p. 1-8, 2011.

LAULAGNIER, K. et al. PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS Lett., v. 572, p. 1-4, 2004.

LAZO, P.A. Functional implications of tetraspanin proteins in cancer biology. Cancer Sci., vol. 98, p. 1666-77, 2007.

LE BITOUX, M.A.; STAMENKOVIC, I. Tumor–host interactions: the role of inflammation. Histochem Cell Biol. v.130, p. 1079-90, 2008.

LE NAOUR, F. et al. Profiling of the tetraspanin web of human colon cancer cells. Mol Cell Proteomics., v. 5, p. 845-57, 2006.

LEE, H.D. et al. Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes. FASEB J., v. 26, p. 3084-9, 2012.

LEE, T.H. Oncogene-dependent survival of highly transformed cancer cells under conditions of extreme centrifugal force - implications for studies on extracellular vesicles. Cell Mol Biol. Lett. v.20, n.1, p.117-29, 2015.

LEWIS, C.E. et al. Cytokine regulation of angiogenesis in breast cancer: the role of tumor- associated macrophages. J. Leukoc. Biol., v. 57, p. 747-51, 1995.

LEWIS, C.E.; POLLARD, J.W. Distinct role of macrophages in different tumor microenvironments. Cancer Res., v. 66, p. 605-12, 2006.

LI, J. et al. Serum-free culture alters the quantity and protein composition of neuroblastoma- derived extracellular vesicles. J. Extracell. Vesicles. v.4, p. 1-12, 2015.

LIU, S.Y.; CHANG, L.C.; PAN, L.F. et al. Clinicopathologic significance of tumor cell-lined vessel and microenvironment in oral squamous cell carcinoma. Oral Oncol., v. 44, p. 277-85, 2008.

LOBB, R..J. et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J. Extracell. Vesicles. v.4, p.1-11, 2015.

LOBERT, V.H. et al. Ubiquitination of alpha 5 beta 1 integrin controls fibroblast migration through lysosomal degradation of fibronectin integrin complexes. Dev. Cell, v. 19, p. 148-59, 2010.

LUZIO J.P; PRYOR P.R.; BRIGHT N.A. Lysosomes: fusion and function. Nat. Rev. Mol. Cell Biol. v.8, n.8, p.622-32, 2007.

MADISON, M.N. Human semen contains exosomes with potent anti-HIV-1 activity. Retrovirology, v. 11, p. 1-15, 2014.

MALKOSKI S.P. et al. Loss of transforming growth factor beta type II receptor increases aggressive tumor behavior and reduces survival in lung adenocarcinoma and squamous cell carcinoma. Clin. Cancer Res. v.18, n.8, p.2173-83, 2012.

MANTOVANI, A. Cancer: inflaming metastasis. Nature, v. 457, p. 36-37, 2009.

MANTOVANI, A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes.Trends Immunol. v. 23, n. 11, p.549-55, 2002. MANTOVANNI, A. et al. Cancer-related inflammation. Nature, v. 454, p. 436-44, 2008. MARGADANT, C. et al. Mechanisms of integrin activation and trafficking. Curr.Opin. Cell Biol., v. 23, p. 607-14, 2011.

MASSAGUÉ J.; SEOANE J.; WOTTON D. Smad transcription factors. Genes and Dev., vol. 19, no. 23, pp. 2783–2810, 2005.

MASSAGUÉ, J. TGF in cancer. Cell. v.134, n.2, p. 215–230, 2008.

MATHIAS R.A.; GOPAL S.K.; SIMPSON R.J. Contribution of cells undergoing epithelial- mesenchymal transition to the tumour microenvironment. J Proteomics. v.14, n.78, p.545-57, 2012.

MENCK K., et al. Induction and transport of Wnt 5a during macrophage-induced malignant invasion is mediated by two types of extracellular vesicles. Oncotarget. v.4, n.11, p. 2057-66, 2013.

MINCIONE G. et al. Loss of expression of TGF-beta1, TbetaRI, and TbetaRII correlates with differentiation in human oral squamous cell carcinomas. Int. J. Oncol. v.32, n.2, p.323-31, 2008.

MIROSLAW J. et al., Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor- 1. Haematol. v.96, n.9, p. 1302-09, 2011.

MORI, K. et al. Infiltration of M2 tumor-associated macrophages in oral squamous cell carcinoma correlates with tumor malignancy. Cancer., v. 3, p. 3726-39, 2011.

NISHIUCHI R. et al. Potentiation of the ligand-binding activity of integrin alpha3beta1 via association with tetraspanin CD151. Proc. Natl. Acad. Sci USA. v.102, n.6, p.1939-44, 2005. NURMENNIEMI, S. et al. A novel organotypic model mimics the tumor microenvironment. Am J Pathol. v.175, n.3, p.1281-9, 2009.

NYSTRÖM M. L. et al. Development of a quantitative method to analyse tumour cell invasion in organotypic culture. J. Pathol. v.205, p.468–75, 2005.

OHNO, Y. et al. Correlation of histological localization of tumor-associated macrophages with clinicopathological features in endometrial cancer. Anticancer Res., v. 24, p. 3335-42, 2004. ONUCHIC, A.C.; CHAMMAS, R. Câncer e o microambiente tumoral. Ver. Med., v.1, n. 89, p. 21-31, 2010.

OUTZEN, H.C.; CUSTER, R.P. Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse. J Natl Cancer Inst. v.55, p.1461-6, 1975. PANT, S.; HILTON, H.; BURCZYNSK, I.M.E. The multifaceted exosome:biogenesis, role in normal and a berrant cellular function, and frontiers for pharmacological and biomarker opportunities. Biochem Pharmacol., v. 83, p. 1484-94, 2012.

PAPAGEORGIS, P. TGF-� Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis. Journal of Oncol., v. 2015, p. 1-15, 2014.

PATEL, R.S.; CLARK, J.R. et al. Prognostic factors in the surgical treatment of patients with oral carcinoma. ANZ J Surg, v. 79, p. 19-22, 2009.

PAULIS L.E. et al. Dendritic cell-based nanovaccines for cancer immunotherapy. Curr. Opin. Immunol. v.25, n.3, p.389-95, 2013.

PEINADO H. et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro- metastatic phenotype through MET. Nat. Med. v.18, p.883-91, 2012.

PELLINEN, T.; IVASKA, J. Integrin traffic. J. Cell Sci., v. 119, p. 3723-31, 2009.

PICKUP, M., NOVITSKIY S; MOSES H. L. The roles of TGF� in the tumour microenvironment. Nature Rev. Cancer, v. 13, n. 11, pp. 788–99, 2013.

PIRILÄ, E. et al. Macrophages Modulate Migration and Invasion of Human Tongue Squamous Cell Carcinoma. PLoS ONE v.10, n.3, e0120895, 2015. DOI:10.1371/journal.

POLLARD, J.W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer., v. 4, p. 71–8, 2004.

POLS M.S.; KLUMPERMAN J. Trafficking and function of the tetraspanin CD63. Exp. Cell Res. v.315, n.9, p.1584-92, 2008.

QUAI, D.F.; JOYCE, J.A. Microenvironmental regulation of tumor progression and metastasis. Nature Medicine, v. 19, n. 11, p. 1423-1437, 2013.

RAMESH, S. et al. Transforming growth factor � (TGF-�)-induced apoptosis: the rise & fall of Bim. Cell Cycle., vol. 8, n. 1, p. 11-17, 2009.

RAPOSO G.; STOORVOGEL W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. v.200, 4, p.373-83, 2013.

ROLNY, C. et al. The tumor suppressor semaphorin 3B triggers a prometastatic program mediated by interleukin 8 and the tumor microenvironment. J. Exp. Med., v. 205, p. 1155-71, 2005.

RUNZ, S. Malignant ascitesderived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol. v.107, p.563–571, 2007.

SANGALETTI, S. et al. Macrophage-Derived SPARC Bridges Tumor Cell-Extracellular Matrix Interactions toward Metastasis. Cancer Res., v. 68, p. 9050–9, 2008.

SANO, D.; MYERS, J.F. Metastasis of squamous cell carcinoma of the oral tongue. Cancer Metastasis Rev., v. 26, p. 645-662, 2007.

SCHREIBER, R.D. Cancer vaccines 2004 opening address: the molecular and cellular basis of cancer immunosurveillance and immunoediting. Cancer Immun. v.5, Suppl 1, p.1-8, 2005. SCHWAB A. et al. Extracellular vesicles from infected cells: potential for direct pathogenesis. Front. Microbiol. v.6, p.11-32, 2015.

SCULLY A. C.; BAGAN B. J. Oral squamous cell carcinoma overview. Oral Oncol. v.45, p.301–8, 2009.

SHANKARAN, V. et al. IFN gamma and lymphocyte sprevent primary tumour development and shape tumour immunogenicity. Nature, v. 410, p. 1107–11, 2001.

SICA, A. et al. Autocrine production of IL-10 mediates defective IL-12 production and NF-κB activation in tumor-associated macrophages. J. Immunol., v.164, n.2 p. 762-7, 2000.

SICA, A.; ALLAVENA, P.; MANTOVANI, A. Cancer related inflammation: The macrophage connection. Cancer Letters, v. 264, p. 204-15, 2008.

SOKI, F.N. et al. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor8 (MFG-E8) –mediated efferocytosis. J Biol Chem, v. 289, p. 24560-72, 2014.

SPIRO, R.H.; STONG, E.W. Surgical treatment of cancer of the tongue. Surg Clin North Am, v. 54, p. 759-65, 1974.

STREET J. M., et al. Identification and proteomic profiling of exosomes in human cerebro spinal fluid. J Transl Med v.10, p. 1-7, 2012.

SUGIMURA, K. et al. High infiltration of tumor-associated macrophages is associated with a poor response to chemotherapy and poor prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer. J. Surg. Oncol. v.111, n.6, 752-9, 2015.

SZCZEPANSKI, M. J. et al., Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor- 1. Haematologica., v. 9, p. 1302-09, 2011.

TANAKA T, et al. Selective inhibition of nuclear factor-κB by nuclear factor-κB essential modulator-binding domain peptide suppresses the metastasis of highly metastatic oral squamous cell carcinoma. Cancer Sci. v. 103, n. 3, p. 455-63, 2012.

TAYLOR, D.D.; GERCEL-TAYLOR, C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol., v. 110, p. 13-21, 2008.

THÉRY, C.; ZITVOGEL, L.; AMIGORENA, S. Exosomes: composition, biogenesis and function. Nat Rev Immunol, v. 2, p. 569-79, 2002.

TJIU, J-W. et al. Tumor-Associated Macrophage-Induced Invasion and Angiogenesis of Human Basal Cell Carcinoma Cells by Cyclooxygenase-2 Induction. J. Investig. Dermatol. v.129, p.1016–25, 2009.

TJIU, J.W. et al. Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J Invest Dermatol., v. 129, p. 1016- 25, 2009.

TRAN TH. et al. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases. Clin Immunol. v.160, n.1, 46-58, 2015.

VAN DEUN, J. et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J. Extracell. Vesicles. .v3. p.248-58, 2014.

VAN GINDERACHTER, J.A. et al. Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology, v. 211, p. 487-501, 2006.

VAN MEEL E.; KLUMPERMAN J. Imaging and imagination: understanding the endo- lysosomal system. Histochem. Cell Biol. v.129, n.3, p.253-66, 2008.

WAKEFIELD, L.M.; HILL, C.S. Beyond TGF-�: roles of other TGF-� super family members in cancer. Nature Reviews Cancer, vol. 13, p. 328-41, 2013.

WIPFF, P.J. et al. Myofibroblast contraction activates latent TGF-�1 from the extracellular matrix. The Journal of Cell Biology, v. 179, n. 6, p. 1311-23, 2007.

WITZ, I.P. Yin-yang activities and vicious cycles in the tumor microenvironment. Cancer Res., v. 68, p. 9-13, 2008.

WOOLGAR, J.A. Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma (Review). Oral Oncol., v. 42, p. 229-39, 2006.

WYCKOFF, J.B., et al. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. v.67, n.6, p-2649-56, 2007.

YAMASHITA, T. et al. Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur. J. Pharm. Biopharm. v. 98, p.1–8, 2016.

YANG, M. et al. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer v. 10, n. 115, p. 1-13, 2011.

YANG, M. et al., Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Cancer, v. 10, p. 1-13, 2011.

YU, Q.; STAMENKOVIC, I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-� and promotes tumor invasion and angiogenesis. Genes and Development., v. 14, p. 163-76, 2000.

YUEN, A.P.W.; LAM, K.Y.; LAM, L.K. et al. Prognostic factors clinically stage I and II oral tongue carcinoma – a comparative study of stage, thickness, shape, growth pattern, invasive front malignancy grading, Martinez– Gimeno score and pathologic features. Head Neck., v. 24, p. 513-20, 2002.

ZHANG, B. et al. Immuno therapeutic potential of extracellular vesicles. Front Immunol, v. 5, n. 518, p. 1-11, 2014.

ZHANG, H.G.; GRIZZLE, W.E. Exosomes and cancer: a newly described pathway of immune suppression. Clin. Cancer Res., v. 17, p. 959-64, 2011.

ZHANG, Y.; WANG, X-F. A niche role for cancer exosomes in metastasis. Nat. Cell Biol. v.17, n.6, p.709-711, 2015.

ZINI, A.; CZERNINSKI, R.; SAGAN-COHEN, H. Oral cancer over four decades: epidemiology, trends, histology, and survival by anatomical sites. J Oral Pathol Med., v. 39, p. 299-305, 2010.

ZITVOGEL, L.; TESNIERE, A.; KROEMER, G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat. Rev. Immunol. v.6, n.10, 715-27, 2006. ZLOTOGORSKI-HURVITZ, A., et al. Human saliva-derived exosomes: comparing methods of isolation. J. Histochem. Cytochem. v.63, n.3, p.181-9.

Documentos relacionados