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Extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) as regulators of tumor–host interaction in a spontaneous metastasis model in rats

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Abstract

EMMPRIN has a role in invasion and metastasis through the induction of MMPs and the consequent modulation of cell-substrate and cell–cell adhesion processes. The present study evaluates the expression of EMMPRIN protein and MMP-2/9 activity in tumor and parenchymal cells in a spontaneous metastasis model in rats. Moreover, we explore the regulation of EMMPRIN and MMP-9 by tumor-epithelial cell interactions in vitro. By zymography, we observed an increased proMMP-9 expression in both metastasized liver and spleen samples from tumor bearing rats. Immunohistochemical studies showed EMMPRIN-positive tumor cells in tumor biopsies as well as in spleen and liver samples from tumor bearing rats. Interestingly, a significant increase in EMMPRIN expression in hepatic cells was also detected. The regulation of EMMPRIN expression in tumor and liver cells in response to tumor–host interaction was investigated in vitro through a tumor cell line culture on extracellular matrix (ECM) molecules or in co-culture with normal rat liver cells (BRL3A cells). No significant changes in EMMPRIN expression were detected in tumor cells cultured on ECM molecules. On the other hand, EMMPRIN protein and MMP-9 mRNA expression were induced in BRL3A cells. The increase in EMMPRIN expression in BRL3A cells was inhibited by an anti-EMMPRIN antibody. These results reinforce the main role of EMMPRIN mediating tumor–host interactions that may evolve new opportunities for therapeutic interventions.

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Acknowledgments

This work was supported by grants from Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba (SECyT), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and Agencia Nacional de Promoción Ciencia y Técnica (FONCyT). S·S. is a Fellow at CONICET. CGP is an established researcher at CONICET.

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Authors and Affiliations

  1. Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina

    Ana Carolina Donadio, María Mónica Remedi, Sebastián Susperreguy, Silvia Frede, Mónica Beatriz Gilardoni & Claudia Gabriela Pellizas

  2. Centocor Inc., Malvern, Pennsylvania, USA

    Yi Tang & Li Yan

  3. School of Oncology, Peking University, Beijing Cancer Hospital, Beijing, China

    Li Yan

Authors
  1. Ana Carolina Donadio
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  2. María Mónica Remedi
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  3. Sebastián Susperreguy
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  4. Silvia Frede
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  5. Mónica Beatriz Gilardoni
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  6. Yi Tang
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  7. Claudia Gabriela Pellizas
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  8. Li Yan
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Correspondence to Ana Carolina Donadio.

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Donadio, A.C., Remedi, M.M., Susperreguy, S. et al. Extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinases (MMPs) as regulators of tumor–host interaction in a spontaneous metastasis model in rats. Histochem Cell Biol 130, 1155–1164 (2008). https://doi.org/10.1007/s00418-008-0496-6

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