Title

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

Authors

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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