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Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells

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Abstract

Introduction

Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines.

Materials and methods

Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey′s post hoc tests were performed.

Results

Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs.

Conclusions

We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

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Acknowledgments

This work was partially supported by grants to Dr. Juan Carlos Calvo (PIP 2010-2012); Dr. Virginia Pistone Creydt (PIP 2011-2013) from CONICET; and Honorio Bigand Fundation.

Conflict of interest

None.

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Authors and Affiliations

  1. Instituto de Biología y Medicina Experimental (IByME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Vuelta de Obligado 2490, C1428DN, Buenos Aires, Argentina

    Virginia Pistone Creydt, Sabrina Johanna Fletcher, Jimena Giudice, Ariana Bruzzone, Norma Alejandra Chasseing, Paula Alejandra Sacca & Juan Carlos Calvo

  2. Instituto de Oncología “Ángel H. Roffo”, Universidad de Buenos Aires, Buenos Aires, Argentina

    Eduardo Gustavo Gonzalez

  3. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    Juan Carlos Calvo

Authors
  1. Virginia Pistone Creydt
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  2. Sabrina Johanna Fletcher
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  3. Jimena Giudice
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  4. Ariana Bruzzone
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  5. Norma Alejandra Chasseing
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  7. Paula Alejandra Sacca
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  8. Juan Carlos Calvo
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Correspondence to Juan Carlos Calvo.

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Pistone Creydt, V., Fletcher, S.J., Giudice, J. et al. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells. Clin Transl Oncol 15, 124–131 (2013). https://doi.org/10.1007/s12094-012-0896-x

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  • DOI: https://doi.org/10.1007/s12094-012-0896-x

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