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1. Proteomic approaches identify members of cofilin pathway involved in oral tumorigenesis.

Author

Giovana M Polachini, Lays M Sobral, Ana M C Mercante, Adriana F Paes-Leme, Flávia C A Xavier, Tiago Henrique, Douglas M Guimarães, Alessandra Vidotto, Erica E Fukuyama, José F Góis-Filho, Patricia M Cury, Otávio A Curioni, Pedro Michaluart, Adriana M A Silva, Victor Wünsch-Filho, Fabio D Nunes, Andréia M Leopoldino, and Eloiza H Tajara

Subjects
Medicine, Science
Abstract

The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.

Published
2012
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2. Genomics and proteomics approaches to the study of cancer-stroma interactions

Author

Flávia C, Rodrigues-Lisoni, Paulo, Peitl, Alessandra, Vidotto, Giovana M, Polachini, José V, Maniglia, Juliana, Carmona-Raphe, Bianca R, Cunha, Tiago, Henrique, Caique F, Souza, Rodrigo A P, Teixeira, Erica E, Fukuyama, Pedro, Michaluart, Marcos B, de Carvalho, Sonia M, Oliani, Eloiza H, Tajara, P M, Cury, M B, de Carvalho, E, Dias-Neto, D L A, Figueiredo, E E, Fukuyama, J F, Góis-Filho, A M, Leopoldino, R C M, Mamede, P, Michaluart-Junior, R A, Moyses, F G, Nóbrega, M P, Nóbrega, F D, Nunes, E F B, Ojopi, L N, Serafini, P, Severino, A M A, Silva, W A, Silva, N J F, Silveira, S C O M, Souza, E H, Tajara, V, Wünsch-Filho, A, Amar, C M, Bandeira, M A, Braconi, L G, Brandão, R M, Brandão, A L, Canto, M, Cerione, R, Cicco, M J, Chagas, H, Chedid, A, Costa, B R, Cunha, O A, Curioni, C S, Fortes, S A, Franzi, A P Z, Frizzera, D, Gazito, P E M, Guimarães, C M, Kaneto, R V M, López, R, Macarenco, M R, Magalhães, C, Meneses, A M C, Mercante, D G, Pinheiro, G M, Polachini, A, Rapoport, C O, Rodini, F C, Rodrigues-Lisoni, R V, Rodrigues, L, Rossi, A R D, Santos, M, Santos, F, Settani, F A M, Silva, I T, Silva, T B, Souza, E, Stabenow, J T, Takamori, P J, Valentim, A, Vidotto, F C A, Xavier, F, Yamagushi, M L, Cominato, P M S, Correa, G S, Mendes, R, Paiva, O, Ramos, C, Silva, M J, Silva, M V C, Tarlá, Faculdade de Medicina de São José do Rio Preto (FAMERP), Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), Arnaldo Vieira de Carvalho Hosp, and Heliopolis Hosp

Subjects
lcsh:Internal medicine, Stromal cell, lcsh:QH426-470, Proteome, Down-Regulation, Apoptosis, Biology, Proteomics, Paracrine signalling, Gene expression, Research article, Genetics, medicine, Humans, Vimentin, Genetics(clinical), Electrophoresis, Gel, Two-Dimensional, Annexin A5, lcsh:RC31-1245, Genetics (clinical), Cell Proliferation, Regulation of gene expression, Tumor microenvironment, Subtraction hybridization, Cancer, Nucleic Acid Hybridization, Genomics, Hep G2 Cells, Fibroblasts, medicine.disease, Molecular biology, Gene Expression Regulation, Neoplastic, lcsh:Genetics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cancer research, Keratins, Mouth Neoplasms, Stromal Cells
Abstract

Made available in DSpace on 2013-08-28T14:07:40Z (GMT). No. of bitstreams: 1 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) Made available in DSpace on 2013-09-30T18:12:07Z (GMT). No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Previous issue date: 2010-05-04 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T14:00:48Z No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Made available in DSpace on 2014-05-20T14:00:48Z (GMT). No. of bitstreams: 2 WOS000278383600001.pdf: 960234 bytes, checksum: 9cd26a9750ec13e67eaf9019e1f48e7b (MD5) WOS000278383600001.pdf.txt: 69473 bytes, checksum: e718db9d53c8e8829f735f82524e401f (MD5) Previous issue date: 2010-05-04 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Rede Proteoma do Estado de São Paulo Ludwig Institute for Cancer Research Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression.Methods: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells.Results: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR.Conclusions: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein. Sch Med FAMERP, Dept Mol Biol, Sao Jose do Rio Preto, Brazil São Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose do Rio Preto, Brazil Sch Med FAMERP, Dept Otorhinolaryngol & Head & Neck Surg, Sao Jose do Rio Preto, Brazil Univ São Paulo, Inst Biociencias, Dept Genet & Evolutionary Biol, São Paulo, Brazil Arnaldo Vieira de Carvalho Hosp, Dept Head & Neck Surg, São Paulo, Brazil Univ São Paulo, Sch Med, Dept Surg, Div Head & Neck Surg, BR-09500900 São Paulo, Brazil Heliopolis Hosp, Dept Head & Neck Surg, São Paulo, Brazil UNESP, Fac Engn Ilha Solteria, Dept Biol & Zootechny, Ilha Solteira, Brazil São Paulo State Univ UNESP, IBILCE, Dept Biol, Sao Jose do Rio Preto, Brazil UNESP, Fac Engn Ilha Solteria, Dept Biol & Zootechny, Ilha Solteira, Brazil FAPESP: 04/12054-9 FAPESP: 06/60162-0 FAPESP: 04/14846-0 FINEP: 01.07.0290.00

Published
2010

3. Differentially expressed proteins in positive versus negative HNSCC lymph nodes

Author

Alessandra Vidotto, Giovana M. Polachini, Marina de Paula-Silva, Sonia M. Oliani, Tiago Henrique, Rossana V. M. López, Patrícia M. Cury, Fabio D. Nunes, José F. Góis-Filho, Marcos B. de Carvalho, Andréia M. Leopoldino, and Eloiza H. Tajara

Subjects
Head and neck carcinoma, Metastasis, Lymph node, Proteomics, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Lymph node metastasis is one of the most important prognostic factors in head and neck squamous cell carcinomas (HNSCCs) and critical for delineating their treatment. However, clinical and histological criteria for the diagnosis of nodal status remain limited. In the present study, we aimed to characterize the proteomic profile of lymph node metastasis from HNSCC patients. Methods In the present study, we used one- and two-dimensional electrophoresis and mass spectrometry analysis to characterize the proteomic profile of lymph node metastasis from HNSCC. Results Comparison of metastatic and non-metastatic lymph nodes showed 52 differentially expressed proteins associated with neoplastic development and progression. The results reinforced the idea that tumors from different anatomical subsites have dissimilar behaviors, which may be influenced by micro-environmental factor including the lymphatic network. The expression pattern of heat shock proteins and glycolytic enzymes also suggested an effect of the lymph node environment in controlling tumor growth or in metabolic reprogramming of the metastatic cell. Our study, for the first time, provided direct evidence of annexin A1 overexpression in lymph node metastasis of head and neck cancer, adding information that may be useful for diagnosing aggressive disease. Conclusions In brief, this study contributed to our understanding of the metastatic phenotype of HNSCC and provided potential targets for diagnostic in this group of carcinomas.

Published
2018
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