Induction of paracrine signaling in metastatic melanoma cells by PPARγ agonist rosiglitazone activates stromal cells and enhances tumor growth
| Autor: | Jürg Hafner, Bao Khanh Trang, Catherine Moret, Mitchell P. Levesque, Helene Moser, Thanh Nhan Nguyen, Liliane Michalik, Christine Goepfert, Pedro Romero, Christine Pich, Patrick Meylan, Camilla Jandus, Romain Loyon, Beatris Mastelic-Gavillet |
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| Přispěvatelé: | University of Zurich, Michalik, Liliane |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Skin Neoplasms Carcinogenesis Angiogenesis T-Lymphocytes Mice SCID Human Umbilical Vein Endothelial Cells/drug effects Monocytes Mononuclear/cytology Mice Macrophages/drug effects 0302 clinical medicine Mice Inbred NOD Monocytes/metabolism Leukocytes 1306 Cancer Research Neoplasm Metastasis Thiazolidinedione Melanoma Melanoma/metabolism/pathology Oligonucleotide Array Sequence Analysis Fibroblasts/metabolism Tumor 10177 Dermatology Clinic PPAR gamma/agonists/metabolism 3. Good health Oncology 030220 oncology & carcinogenesis 2730 Oncology Skin Neoplasms/metabolism/pathology Rosiglitazone medicine.drug T-Lymphocytes/cytology Stromal cell medicine.drug_class Stromal Cells/metabolism Paracrine Communication 610 Medicine & health SCID Rosiglitazone/pharmacology Cell Line 03 medical and health sciences Paracrine signalling Cell Line Tumor Human Umbilical Vein Endothelial Cells medicine Animals Humans Inflammation business.industry Macrophages Angiogenesis Inducing Agents/metabolism Cancer Fibroblasts medicine.disease PPAR gamma 030104 developmental biology Leukocytes Mononuclear Cancer research Inbred NOD Angiogenesis Inducing Agents Stromal Cells business Neoplasm Transplantation |
| Zdroj: | Cancer Research, Vol. 78, No 22 (2018) pp. 6447-6461 |
| ISSN: | 0008-5472 |
| DOI: | 10.5167/uzh-158449 |
| Popis: | In addition to improving insulin sensitivity in type 2 diabetes, the thiazolidinedione family of compounds and the pharmacologic activation of their best-characterized target PPARγ have been proposed as a therapeutic option for cancer treatment. In this study, we reveal a new mode of action for the thiazolidinedione rosiglitazone that can contribute to tumorigenesis. Rosiglitazone activated a tumorigenic paracrine communication program in a subset of human melanoma cells that involves the secretion of cytokines, chemokines, and angiogenic factors. This complex blend of paracrine signals activated nonmalignant fibroblasts, endothelial cells, and macrophages in a tumor-friendly way. In agreement with these data, rosiglitazone promoted human melanoma development in xenografts, and tumors exposed to rosiglitazone exhibited enhanced angiogenesis and inflammation. Together, these findings establish an important tumorigenic action of rosiglitazone in a subset of melanoma cells. Although studies conducted on cohorts of diabetic patients report overall benefits of thiazolidinediones in cancer prevention, our data suggest that exposure of established tumors to rosiglitazone may be deleterious. Significance: These findings uncover a novel mechanism by which the thiazolidinedione compound rosiglitazone contributes to tumorigenesis, thus highlighting a potential risk associated with its use in patients with established tumors. Cancer Res; 78(22); 6447–61. ©2018 AACR. |
| Databáze: | OpenAIRE |
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