title: Simultaneous irradiation of fibroblasts and carcinoma cells repress the secretion of soluble factors able to stimulate carcinoma cell migration.
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.
authors: INSERM U1030, LabEx LERMIT, Villejuif, France; Université Paris Sud, Kremlin-Bicêtre, France; Institut Gustave Roussy, Villejuif, France.
authors: Adnan
authors: A
authors: Arshad
authors: INSERM U1030, LabEx LERMIT, Villejuif, France; Université Paris Sud, Kremlin-Bicêtre, France; Institut Gustave Roussy, Villejuif, France.
authors: Eric
authors: E
authors: Deutsch
authors: 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.
authors: Marie-Catherine
authors: MC
authors: Vozenin
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D002454:Cell Differentiation / Q000528:radiation effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D019899:Paracrine Communication / Q000528:radiation effects; D011827:Radiation; D011836:Radiation Tolerance; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000528:radiation effects; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: D053773:Transforming Growth Factor beta1; D014746:Vimentin; D020741:rho GTP-Binding Proteins
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