Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy Journal Article

Authors: Gilaberte, Y.; Milla, L.; Salazar, N.; Vera-Alvarez, J.; Kourani, O.; Damian, A.; Rivarola, V.; Roca, M. J.; Espada, J.; Gonzalez, S.; Juarranz, A.
Article Title: Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy
Abstract: Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-S-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT.
Keywords: survival; expression; lung-cancer; efficacy; activation; growth-factor receptor; retrospective analysis; kinases; messenger-rna; nonmelanoma skin-cancer; signal-regulated
Journal Title: Journal of Investigative Dermatology
Volume: 134
Issue: 9
ISSN: 0022-202X
Publisher: Nature Publishing Group  
Date Published: 2014-09-01
Start Page: 2428
End Page: 2437
Language: English
ACCESSION: WOS:000340352200021
DOI: 10.1038/jid.2014.178
PUBMED: 24717244
Notes: Article -- Source: Wos
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  1. Salvador Gonzalez Rodriguez
    204 Rodriguez