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Radiother Oncol. 2013 Jul;108(1):162-7. doi: 10.1016/j.radonc.2013.04.001. Epub 2013 Jun 3.

Radiation-induced myosin IIA expression stimulates collagen type I matrix reorganization.

Author information

1
Department of Radiation Oncology and Experimental Cancer Research, Ghent University Hospital, Belgium. stephanie.blockhuys@ugent.be

Abstract

BACKGROUND AND PURPOSE:

Extracellular matrix (ECM) reorganization critically contributes to breast cancer (BC) progression and radiotherapy response. We investigated the molecular background and functional consequences of collagen type I (col-I) reorganization by irradiated breast cancer cells (BCC).

MATERIALS AND METHODS:

Radiation-induced (RI) col-I reorganization was evaluated for MCF-7/6, MCF-7/AZ, T47D and SK-BR-3 BCC. Phase-contrast microscopy and a stressed matrix contraction assay were used for visualization and quantification of col-I reorganization. Cell-matrix interactions were assessed by the inhibition of β1 integrin (neutralizing antibody 'P5D2') or focal adhesion kinase (FAK; GSK22560098 small molecule kinase inhibitor). The role of the actomyosin cytoskeleton was explored by western blotting analysis of myosin II expression and activity; and by gene silencing of myosin IIA and pharmacological inhibition of the actomyosin system (blebbistatin, cytochalasin D). BCC death was evaluated by propidium iodide staining.

RESULTS:

We observed a radiation dose-dependent increase of col-I reorganization by BCC. β1 Integrin/FAK-mediated cell-matrix interactions are essential for RI col-I reorganization. Irradiated BCC are characterized by increased myosin IIA expression and myosin IIA-dependent col-I reorganization. Moreover, RI col-I reorganization by BCC is associated with decreased BCC death, as suggested by pharmacological targeting of the β1 integrin/FAK/myosin IIA pathway.

CONCLUSIONS:

Our data indicate the role of myosin IIA in col-I reorganization by irradiated BCC and reciprocal BCC death.

KEYWORDS:

Actomyosin; Breast cancer; Cell–matrix interactions; Collagen; ECM remodeling; Ionizing radiation

PMID:
23742963
DOI:
10.1016/j.radonc.2013.04.001
[Indexed for MEDLINE]

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