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Loss of Caveolin-1 Expression in Tumor Cells is Associated with Increased Aggressiveness and Cell Invasion in Oral Squamous Cell Carcinoma

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Abstract

Background

Changes in Caveolin-1 (CAV-1) expression are related to tumorigenesis. The aim of this study was to evaluate the role of CAV-1 in tumor progression in oral squamous cell carcinoma (SCC) tissue samples and the effect of CAV-1 silencing on two oral tongue SCC (OTSCC) cell lines (SCC-25, from a primary tumor, and HSC-3 from lymph node metastases).

Methods

Mycroarray hybridization, mRNA expression, and immunohistochemistry were performed on OSCC tissue samples and corresponding non-tumoral margin tissues. The effects of CAV-1 silencing (siCAV-1) on cell viability, membrane fluidity, on the expression of epithelial to mesenchymal transition (EMT) markers and on cell migration and invasion capacity of OTSCC cell lines were evaluated.

Results

Microarray showed a greater CAV-1 expression (1.77-fold) in OSCC tumors than in non-tumoral tissues and 2.0-fold more in less aggressive OSCCs. However, significant differences in CAV-1 gene expression were not seen between tumors and non-tumoral margins nor CAV-1 with any clinicopathological parameters. CAV-1 protein was localized both in carcinoma and in spindle cells of the tumor microenvironment (TME), and CAV-1 positive TME cells were associated with smaller/more aggressive tumors, independent of the carcinoma cells’ expression. Silencing of CAV-1 increased cell viability only in SCC-25 cells. It also stimulated the invasion of HSC-3 cells and increased ECAD and BCAT mRNA in these cells; however, the protein levels of the EMT markers were not affected.

Conclusion

Decreased expression of CAV-1 by tumor cells in OSCC and an increase in the TME were associated with increased cell invasiveness and tumor aggressiveness.

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Acknowledgements

GENCAPO (Head and Neck Genome Project) Consortium for the sample collection and initial processing, clinical data collection, providing histopathological analysis of tissue samples, and the acquisition of informed consent from each patient. We declare the paper was reviewed for grammar and syntax by an English expert.

Funding

This work was supported by the National Council for Scientific and Technological Development (CNPq) [Grant No. 421249/2018–8] and Higher Education Personnel Improvement Coordination (RB Nascimento fellowship—CAPES).

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Authors and Affiliations

  1. Laboratório de Patologia Oral Cirúrgica, Faculdade de Odontologia, Universidade Federal da Bahia, Rua Araújo Pinho, 62, Canela, Salvador, Bahia, 40110-150, Brazil

    Rebeca Barros Nascimento & Flávia Caló Aquino Xavier

  2. Laboratório de Biologia da Matriz Extracelular e Interação Celular, Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil

    Katiúcia Batista Silva Paiva & Luiz Henrique Santos Silva

  3. Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, Oulu, Finland

    Maija Risteli & Tuula Anneli Salo

  4. Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland

    Maija Risteli & Tuula Anneli Salo

  5. Departamento de Ciências Biológicas, Faculdade de Odontologia de Bauru, Universidade de São Paulo, Bauru, Brazil

    Camila Oliveira Rodini

  6. Programa de Pós-Graduação em Biofotônica Aplicada a Ciências da Saúde, Universidade Nove de Julho, UNINOVE, São Paulo, Brazil

    Maria Fernanda Setúbal Destro Rodrigues

  7. Departamento de Cirurgia de Cabeça e Pescoço, Instituto de Câncer Doutor Arnaldo Vieira de Carvalho, São Paulo, Brazil

    Rafael De Cicco

  8. Centro de Pesquisa Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil

    Rossana Verónica Mendoza Lopez

  9. Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland

    Tuula Anneli Salo

  10. Department of Pathology, HUSLAB, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland

    Tuula Anneli Salo

  11. Laboratório de Patologia Molecular, Faculdade de Odontologia, Universidade de São Paulo, São Paulo, Brazil

    Fábio Daumas Nunes

Authors
  1. Rebeca Barros Nascimento
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  2. Katiúcia Batista Silva Paiva
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Contributions

All authors have contributed to this article as follow: RBN performed all the in vitro experiments, analysis, data interpretation, and wrote the initial draft of the manuscript. MJ and TAS designed the in vitro experiments and data interpretation. LHSS performed IHC experiments. KBSP, MFSDR, COR, FCAX performed the microarray and qRT-PCR and their analysis of tumor samples. FCAX and FDN analysed IHC images and statistical analysis. RDC, RVML and FDN are members of GENCAPO and collected the tissue samples and clinical data. FCAX, KBSP and TAS were the advisors of RBN PhD thesis. All authors have reviewed and approved the final version.

Corresponding author

Correspondence to Flávia Caló Aquino Xavier.

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“All procedures performed in studies involving human participants were in accordance with the ethical standards of the Brazilian National Ethics Committee (Process #16491) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Nascimento, R.B., Paiva, K.B.S., Risteli, M. et al. Loss of Caveolin-1 Expression in Tumor Cells is Associated with Increased Aggressiveness and Cell Invasion in Oral Squamous Cell Carcinoma. Head and Neck Pathol 17, 618–630 (2023). https://doi.org/10.1007/s12105-023-01562-w

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