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Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer

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Abstract

Under many circumstances, the host constituents that are found in the tumor microenvironment support a malignancy network and provide the cancer cells with advantages in proliferation, invasiveness and metastasis establishment at remote organs. It is known that Toll like receptors (TLRs) are expressed not only on immune cells but also on cancer cells and it has suggested a deleterious role for TLR3 in inflammatory disease. Hypothesizing that altered IFNγ signaling may be a key mechanism of immune dysfunction common to cancer as well CXCR4 is overexpressed among breast cancer patients, the mRNA expression of TLR3, CXCR4 and IFNγ in breast cancer tumor tissues was investigated. No statistically significant differences in the expression of CXCR4 mRNA, IFNγ and TLR3 between healthy and tumor tissues was observed, however, it was verified a positive correlation between mRNA relative expression of TLR3 and CXCR4 (p < 0.001), and mRNA relative expression of TLR3 was significantly increased in breast cancer tumor tissue when compared to healthy mammary gland tissue among patients expressing high IFNγ (p = 0.001). Since the tumor microenvironment plays important roles in cancer initiation, growth, progression, invasion and metastasis, it is possible to propose that an overexpression of IFNγ mRNA due to the pro-inflammatory microenvironment can lead to an up-regulation of CXCR4 mRNA and consequently to an increased TLR3 mRNA expression even among nodal negative patients. In the future, a comprehensive study of TLR3, CXCR4 and IFNγ axis in primary breast tumors and corresponding healthy tissues will be crucial to further understanding of the cancer network.

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Acknowledgments

The authors would like to acknowledge the volunteers who made this study possible and the Cancer Institute of Londrina, PR, Brazil for their collaboration. This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), the Fundação Araucária (PPSUS) and the Londrina State University Graduate Administration (PROPPG-UEL). Doctoral post graduate student, Marla Karine Amarante is a fellow of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. The authors would like to express their gratitude to GENOPAR for supplying laboratory equipment. The entire article was revised by British-born scientific editor.

Conflict of interest

The authors declare to comply with all requirements for publication there are no conflict of interest.

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Authors and Affiliations

  1. Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, Londrina, PR, CEP 86051-970, Brazil

    Marla Karine Amarante, Karen Brajão de Oliveira, Roberta Losi Guembarovski, Ana Cristina da Silva do Amaral Herrera & Maria Angelica Ehara Watanabe

  2. Department of Oncology, Cancer Institute of Londrina, Londrina, PR, Brazil

    Ana Cristina da Silva do Amaral Herrera

  3. Department of Pathology, Healthy Sciences Center, State University of Londrina, Londrina, PR, Brazil

    Alda Losi Guembarovski

  4. Gineco-Med Clinical Laboratory of Mastology, Londrina, PR, Brazil

    Walter Jorge Sobrinho

  5. Division of Clinical Immunology, Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Julio Cesar Voltarelli

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  1. Marla Karine Amarante
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  2. Karen Brajão de Oliveira
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  8. Maria Angelica Ehara Watanabe
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Correspondence to Marla Karine Amarante.

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Amarante, M.K., de Oliveira, K.B., Guembarovski, R.L. et al. Toll-like receptor 3: implications for proinflammatory microenvironment in human breast cancer. Mol Biol Rep 39, 11087–11092 (2012). https://doi.org/10.1007/s11033-012-2013-1

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  • DOI: https://doi.org/10.1007/s11033-012-2013-1

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