Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions

    Authors

    L. Alili; M. Sack; A. S. Karakoti; S. Teuber; K. Puschmann; S. M. Hirst; C. M. Reilly; K. Zanger; W. Stahl; S. Das; S. Seal;P. Brenneisen

    Comments

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    Abbreviated Journal Title

    Biomaterials

    Keywords

    Antioxidant; Carcinogenesis; Cell culture; Tumor-stroma interactions; Fibroblast; Nanoparticle; HUMAN DERMAL FIBROBLASTS; JUNCTIONAL INTERCELLULAR COMMUNICATION; CANCER-CELLS; OXIDE NANOPARTICLES; NANOCERIA; CERIUM; ANTIOXIDANT; EXPRESSION; TOXICITY; DAMAGE; Engineering, Biomedical; Materials Science, Biomaterials

    Abstract

    Tumor-stroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal for tumor progression, populate the microecosystem of reactive stroma. The formation of myofibroblasts is mediated by tumor derived transforming growth factor beta 1 (TGF beta 1) which initiates a reactive oxygen species cell type dependent expression of alpha-smooth muscle actin, a biomarker for myofibroblastic cells. Myofibroblasts express and secrete proinvasive factors significantly increasing the invasive capacity of tumor cells via paracrine mechanisms. Although antioxidants prevent myofibroblast formation, the same antioxidants increase the aggressive behavior of the tumor cells. In this study, the question was addressed of whether redox-active polymer-coated cerium oxide nanoparticles (CNP, nanoceria) affect myofibroblast formation, cell toxicity, and tumor invasion. Herein, nanoceria downregulate both the expression of alpha-smooth muscle actin positive myofibroblastic cells and the invasion of tumor cells. Furthermore, concentrations of nanoceria being non-toxic for normal (stromal) cells show a cytotoxic effect on squamous tumor cells. The treatment with redox-active CNP may form the basis for protection of stromal cells from the dominating influence of tumor cells in tumor-stroma interaction, thus being a promising strategy for chemoprevention of tumor invasion. (C) 2011 Elsevier Ltd. All rights reserved.

    Journal Title

    Biomaterials

    Volume

    32

    Issue/Number

    11

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    2918

    Last Page

    2929

    WOS Identifier

    WOS:000288465800022

    ISSN

    0142-9612

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