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Laminin-derived peptide AG73 regulates migration, invasion, and protease activity of human oral squamous cell carcinoma cells through syndecan-1 and β1 integrin

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Tumor Biology

Abstract

Squamous cell carcinoma is a prevalent head and neck tumor with high mortality. We studied the role played by laminin α1 chain peptide AG73 on migration, invasion, and protease activity of cells (OSCC) from human oral squamous cell carcinoma. Immunohistochemistry and immunofluorescence analyzed expression of laminin α1 chain and MMP9 in oral squamous cells carcinoma in vivo and in vitro. Migratory activity of AG73-treated OSCC cells was investigated by monolayer wound assays and in chemotaxis chambers. AG73-induced invasion was assessed in Boyden chambers. Invasion depends on MMPs. Conditioned media from cells grown on AG73 was subjected to zymography. We searched for AG73 receptors related to these activities in OSCC cells. Immunofluorescence analyzed AG73-induced colocalization of syndecan-1 and β1 integrin. Cells had these receptors silenced by siRNA, followed by treatment with AG73 and analysis of migration, invasion, and protease activity. Oral squamous cell carcinoma expresses laminin α1 chain and MMP9. OSCC cells treated with AG73 showed increased migration, invasion, and protease activity. AG73 induced colocalization of syndecan-1 and β1 integrin. Knockdown of these receptors decreased AG73-dependent migration, invasion, and protease activity. Syndecan-1 and β1 integrin signaling downstream of AG73 regulate migration, invasion, and MMP production by OSCC cells.

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Acknowledgments

This investigation was supported by The State of São Paulo Research Foundation (FAPESP grants 2006/57079-4 and 2008/57103-8) and Brazilian National Council for Scientific and Technological Development (CNPq grants 471751/2003-0, 304868/2006-0 and 470622/2007-5). Adriane S. Siqueira and Letícia N. Gama-de-Souza are recipients of Graduate fellowships from FAPESP (2007/51950-8 and 2005/55602-9). João J. V. Pinheiro is recipient of a Post Doctoral fellowship from CNPq (504667/2008-4).

Conflict of Interest Statement

None declared

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes,1524 Ed. Biomédicas 1, sala 302, São Paulo, SP, 05508-000, Brazil

    Adriane S. Siqueira, Letícia N. Gama-de-Souza, João J. V. Pinheiro & Ruy G. Jaeger

  2. Department of Morphology, Center for Health Sciences (CCS), Federal University of Espírito Santo, Vitória, Av. Fernando Ferrari 514, Vitoria, ES, 29075-910, Brazil

    Letícia N. Gama-de-Souza

  3. Department of Histopathology, Ophir Loyola Cancer Hospital, Av. Magalhães Barata, 992, Belém, PA, 66062-240, Brazil

    Maria Vanda C. Arnaud

  4. Department of Oral Pathology, School of Dentistry, Federal University of Pará, Rua dos Mundurucus, 4487, Belém, PA, 66073-000, Brazil

    João J. V. Pinheiro

  5. Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes,1524, Ed Biomédicas 1, sala 302, São Paulo, SP, 05508-000, Brazil

    Ruy G. Jaeger

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  1. Adriane S. Siqueira
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  2. Letícia N. Gama-de-Souza
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Correspondence to Ruy G. Jaeger.

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Siqueira, A.S., Gama-de-Souza, L.N., Arnaud, M.V.C. et al. Laminin-derived peptide AG73 regulates migration, invasion, and protease activity of human oral squamous cell carcinoma cells through syndecan-1 and β1 integrin. Tumor Biol. 31, 46–58 (2010). https://doi.org/10.1007/s13277-009-0008-x

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