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

RODRIGUEZ, LUCÍA BELEN; VILCHES, MARÍA LAURA; MILLA, LAURA; PRUCCA, CESAR; LAMBERTI, MARÍA JULIA; PALACIOS, RODRIGO E.; CAPUTTO, BEATRIZ; RIVAROLA, VIVIANA A.

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Photodynamic therapy (PDT) is an oncologic treatment. It is based on the administration of a photosensitizer and its activation through visible light. It is mainly employed to treat skin, bladder, oesophagus and lung cancer. An innovator PDT application is for human glioblastoma multiforme (GBM). The main problem of all anticancer therapies is the recidivism caused by resistant cells. It is proposed that only a small proportion of neoplastic cells, called cancer stem cells (CSC), have the capacity to generate a tumour and resist to oncologic treatments. The objective of the present investigation was determinate if PDT-Me-ALA (pro-drug) resistant cells of T98G and SCC lines have CSC characteristics, as a first step to further search of therapeutic targets. There were determinated in resistant cells, comparing with parental cells (non submitted to PDT): the tumorigenic capacity (immune-depressed mice), the growth ability in 3D cultures (spheroids), the intracellular photosensitizer accumulation after Me-ALA incubation (fluorescence microscopy, flow citometry and spectrofluorometry) and the cell viability after PDT employing ALA and Me-ALA. The resistant population showed CSC characteristics, such as higher tumorigenic capacity, spheroids with higher viability, size and number of cells, lower photosensitizer drug accumulation and higher viability after PDT, respect to parental cells. These results motivated us to continue this investigation studying the CSC molecular ways with the aim to find possible therapeutic targets to enhance the PDT efficacy.