Cancer stem cells in the resistance to photodynamic therapy in human glioblastoma multiforme and squamous carcinoma

RODRIGUEZ, LB; VILCHEZ ML; MILLA L; PRUCCA C; LAMBERTI MJ; PALACIOS R; CAPUTTO B; RUMIE VITTAR NB*, LAMBERTI MJ*, PANSA MF*, VERA RE, RODRIGUEZ ME, COGNO IS, MILLA SANABRIA LN, RIVAROLA VA

Congreso; SAIC; 2016

Photodynamic therapy (PDT) is an oncologic treatment. It isbased on the administration of a photosensitizer and its activationthrough visible light. It is mainly employed to treat skin, bladder,oesophagus and lung cancer. An innovator PDT application is forhuman glioblastoma multiforme (GBM). The main problem of allanticancer therapies is the recidivism caused by resistant cells. Itis proposed that only a small proportion of neoplastic cells, calledcancer stem cells (CSC), have the capacity to generate a tumourand resist to oncologic treatments. The objective of the present investigationwas determinate if PDT-Me-ALA (pro-drug) resistant cells of T98G and SCC lines have CSC characteristics, as a first step to furthersearch of therapeutic targets. There were determinated inresistant cells, comparing with parental cells (non submitted to PDT):the tumorigenic capacity (immune-depressed mice), the growthability in 3D cultures (spheroids), the intracellular photosensitizeraccumulation after Me-ALA incubation (fluorescence microscopy,flow citometry and spectrofluorometry) and the cell viability after PDTemploying ALA and Me-ALA. The resistant population showed CSCcharacteristics, such as higher tumorigenic capacity, spheroids withhigher viability, size and number of cells, lower photosensitizer drugaccumulation and higher viability after PDT, respect to parental cells.These results motivated us to continue this investigation studyingthe CSC molecular ways with the aim to find possible therapeutictargets to enhance the PDT efficacy.