title: Progression-related loss of stromal Caveolin 1 levels fosters the growth of human PC3 xenografts and mediates radiation resistance.
abstract: Despite good treatment results in localized prostate tumors, advanced disease stages usually have a pronounced resistance to chemotherapy and radiotherapy. The membrane protein caveolin-1 (Cav1) functions here as an important oncogene. Therefore we examined the impact of stromal Cav1 expression for tumor growth and sensitivity to ionizing radiation (IR). Silencing of Cav1 expression in PC3 cells resulted in increased tumor growth and a reduced growth delay after IR when compared to tumors generated by Cav1-expressing PC3 cells. The increased radiation resistance was associated with increasing amounts of reactive tumor stroma and a Cav1 re-expression in the malignant epithelial cells. Mimicking the human situation these results were confirmed using co-implantation of Cav1-silenced PC3 cells with Cav1-silenced or Cav1-expressing fibroblasts. Immunohistochemically analysis of irradiated tumors as well as human prostate tissue specimen confirmed that alterations in stromal-epithelial Cav1 expressions were accompanied by a more reactive Cav1-reduced tumor stroma after radiation and within advanced prostate cancer tissues which potentially mediates the resistance to radiation treatment. Conclusively, the radiation response of human prostate tumors is critically regulated by Cav1 expression in stromal fibroblasts. Loss of stromal Cav1 expression in advanced tumor stages may thus contribute to resistance of these tumors to radiotherapy.
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, Virchowstrasse 173, 45122 Essen, Germany.|Department of Urology and Urooncology, University of Duisburg-Essen, University Hospital, Essen, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Panic
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, Virchowstrasse 173, 45122 Essen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ketteler
authors.affiliation: Institut of Pathology, University of Duisburg-Essen, University Hospital, Hufelandstr. 55, 45122 Essen, Essen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.affiliation: Department of Radiotherapy, University of Duisburg-Essen, University Hospital, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Sak
authors.affiliation: Department of Radiation Oncology, University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Herskind
authors.affiliation: Department of Radiation Oncology, University Hospital, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Maier
authors.affiliation: Department of Urology and Urooncology, University of Duisburg-Essen, University Hospital, Essen, Hufelandstr. 55, 45122 Essen, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, Virchowstrasse 173, 45122 Essen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Jendrossek
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, University Hospital, Virchowstrasse 173, 45122 Essen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Klein
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000528:radiation effects
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1