Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration

Adnan Arshad; Eric Deutsch; Marie-Catherine Vozenin

doi:10.1371/journal.pone.0115447

Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration

PLoS One. 2015 Jan 30;10(1):e0115447. doi: 10.1371/journal.pone.0115447. eCollection 2015.

Authors

Adnan Arshad¹, Eric Deutsch¹, Marie-Catherine Vozenin²

Affiliations

¹ INSERM U1030, LabEx LERMIT, Villejuif, France; Université Paris Sud, Kremlin-Bicêtre, France; Institut Gustave Roussy, Villejuif, France.
² INSERM U1030, LabEx LERMIT, Villejuif, France; Université Paris Sud, Kremlin-Bicêtre, France; Institut Gustave Roussy, Villejuif, France; Laboratoire de recherche en Radio-Oncologie, Service de Radio-Oncologie/département d'Oncologie/CHUV, Lausanne, Switzerland.

Abstract

Stroma mediated wound healing signals may share similarities with the ones produced by tumor's microenvironment and their modulation may impact tumor response to the various anti-cancer treatments including radiation therapy. Therefore we conducted this study, to assess the crosstalk between stromal and carcinoma cells in response to radiotherapy by genetic modulation of the stroma and irradiation. We found that fibroblasts irrespective of their RhoB status do not modulate intrinsic radiosensitivity of TC-1 but produce diffusible factors able to modify tumor cell fate. Then we found that Wt and RhoB deficient fibroblasts stimulated TC-1 migration through distinct mechanisms which are TGF-β1 and MMP-mediated respectively. Lastly, we found that simultaneous irradiation of fibroblasts and TC-1 abrogated the pro-migratory phenotype by repression of TGF-β and MMP secretion. This last result is highly relevant to the clinical situation and suggests that conversely to, the current view; irradiated stroma would not enhance carcinoma migration and could be manipulated to promote anti-tumor immune response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carcinoma / metabolism
Carcinoma / pathology
Carcinoma / radiotherapy*
Cell Differentiation / radiation effects
Cell Line, Tumor
Cell Movement / radiation effects*
Fibroblasts / metabolism
Fibroblasts / pathology
Fibroblasts / radiation effects*
Humans
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Lung Neoplasms / radiotherapy*
Mice
Paracrine Communication / radiation effects
Radiation
Radiation Tolerance
Transforming Growth Factor beta1 / metabolism
Vimentin / metabolism
Wound Healing / radiation effects
rho GTP-Binding Proteins / deficiency
rho GTP-Binding Proteins / genetics*

Substances

Transforming Growth Factor beta1
Vimentin
rho GTP-Binding Proteins

Grants and funding

AA was supported by a Scholarship Grant from Higher Education Commission of Pakistan and Fondation Gustave Roussy. The work was supported by Fondation Gustave Roussy Grant. Inserm U1030 is a member of the Laboratory of Excellence LERMIT supported by a grant from ANR (ANR-10-LABX-33). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.