INVESTIGADORES
CASAS Adriana Gabriela
congresos y reuniones científicas
Título:
Cell adhesion mechanisms involved in resistance to Photodynamic Therapy of Ras-expressing tumors
Autor/es:
RODRIGUEZ L; DI VENOSA G; RIVAS M; MAMONE L; GÁNDARA L; JUARRANZ A; SANZ-RODRIGUEZ F; BATLLE A; CASAS A
Lugar:
Cardiff
Reunión:
Congreso; Porphyrins and Porphyrias 2011; 2011
Institución organizadora:
British Association of Dermatologists
Resumen:
Photodynamic therapy (PDT) is an anticancer
tretament that involves administration of a tumour-localising photosensitizer
and its subsequent activation by visible light to result primarily
in singlet oxygen?induced photodamage to the tumour. The
photosensitizer absorbs light and in the presence of oxygen transfers energy,
producing short-lived cytotoxic oxygen species such as singlet oxygen or other
oxygen radicals.
The
aim of this work was to explain the mechanisms that induce resistance to PDT
observed in previous work in a normal/tumor cell line pair. We employed the
tumor cell line HB4a-ras transfected with the oncogene H-Ras and its parental
normal mammary epithelium cell line HB4a counterpart.
We
analyzed by means of confocal fluorescence microscopy, the subcellular
localization of a panel of photosensitizers: Verteporfirin, Acridine Orange, Foscan, Photofrin II, Chlorin e6 and Merocyanine 540. We did not find significant differences on
subcellular distribution between both cellular lines.
We
have also analyzed the expression of adhesion molecules as well as molecules
related to the processes of multiple resistance to drugs such as survivin
and. We did not find differences between
both cell lines neither in distribution nor in expression of both molecules
employing inmunofluorescence assays and Western Blots techniques.
On
the other hand, we found in both cell lines equal expression of vinculin,
(involved in adhesion to the substratum), actin (cytoskeleton protein), and
E-cadherin (involved in cell-cell adhesion) its subcellular distribution was
different.
We
have also performed tests of cell adhesion to extracellular matrix (ECM)
proteins such as Fibronectin, Collagen I and IV, Vitronectin and Laminin. We
observed that HB4a-Ras cells showed major adhesion than HB4a to all the ECM
proteins except for Vitronectin, which showed equal adhesion to both cell
lines.
In
PDT studies employing cell suspensions of HB4a and its Ras transfected
counterpart, we showed an increased resistance to the phtotodynamic treatment,
showing that cell adhesion is highly involved in the mechanism of
photoresistance.