Characterisation of resistance mechanisms developed by basal cell carcinoma cells in response to repeated cycles of photodynamic therapy
Entidad
UAM. Departamento de Biología; UAM. Departamento de Biología MolecularEditor
Nature Publishing GroupFecha de edición
2019-12-01Cita
10.1038/s41598-019-41313-y
Scientific Reports 9.11 (2019): 4835
ISSN
2045-2322 (Electronic)DOI
10.1038/s41598-019-41313-yProyecto
Gobierno de España. FIS PI15/00974; Gobierno de España. PI18/00708Materias
Aminolevulinic Acid; Animals; Carcinogenesis; Carcinoma, Basal Cell; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Drug Resistance, Neoplasm; Humans; Mice; Mice, Transgenic; Patched-1 Receptor; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Skin Neoplasms; Tumor Suppressor Protein p53; Ultraviolet Rays; Wnt Signaling Pathway; Biología y Biomedicina / BiologíaDerechos
© The Author(s) 2019Resumen
photodynamic therapy (pDt) with methyl-aminolevulinate acid (MAL-pDt) is being used for the treatment of Basal cell carcinoma (BCC), but recurrences have been reported. In this work, we have evaluated resistance mechanisms to MAL-pDt developed by three BCC cell lines (AsZ, BsZ and CsZ), derived from mice on a ptch+/− background and with or without p53 expression, subjected to 10 cycles of PDT (10thG). the resistant populations showed mesenchymal-like structure and diminished proliferative capacity and size compared to the parental (p) cells. the resistance was dependent on the production of the endogenous photosensitiser protoporphyrin IX in the CsZ cell line and on its cellular localisation in AsZ and BsZ cells. Moreover, resistant cells expressing the p53 gene presented lower proliferation rate and increased expression levels of N-cadherin and Gsk3β (a component of the Wnt/β-catenin pathway) than P cells. In contrast, 10thG cells lacking the p53 gene showed lower levels of expression of Gsk3β in the cytoplasm and of e-cadherin and β-catenin in the membrane. In addition, resistant cells presented higher tumorigenic ability in immunosuppressed mice. Altogether, these results shed light on resistance mechanisms of BCC to pDt and may help to improve the use of this therapeutic approach
Lista de ficheros
Google Scholar:Lucena, Silvia Rocío
-
Zamarrón, Alicia
-
Carrasco Cerro, Elisa
-
Marigil, Miguel Ángel
-
Mascaraque Checa, Marta
-
Fernández-Guarino, Montserrat
-
Gilaberte, Yolanda
-
González, Salvador
-
Juarranz de la Fuente, Ángeles
Lista de colecciones del ítem
Registros relacionados
Mostrando ítems relacionados por título, autor, creador y materia.