Changes in actin and E-cadherin expression induced by 5-aminolevulinic acid. Photodynamic Therapy in normal and tumor cell lines

DI VENOSA G, RODRIGUEZ L, MAMONE L, BATLLE A & CASASA.

Bressanone, Italia

Congreso; X Photodynamic Therapy and Photodiagnosis in Clinical Practice; 2008

Photodynamic therapy (PDT) is a promising anticancer treatment based on light-induced destruction of photosensitised malignant cells and tissues. In the last years 5, aminolevulinic acid (ALA), a biochemical precursor of the potent photosensitizer protoporphyrin IX (PpIX), has been successfully used for fluorescent diagnosis and photodynamic treatment of cancer. It has been found that PDT strongly affects cell-cell and cell-substrate adhesion through the reorganization of some cytoskeletal and adhesion proteins. The aim of the present work was to study the changes induced by ALA-PDT treatment on the cytoskeleton actin network and on E-cadherin expression, protein involved in the cell to cell adhesion. We employed the normal mammary luminal epithelial HB4a and its tumour counterpart transfected with the oncogene H-Ras (VAL/12 Ras) as a model of normal/tumour cells. In previous work we have shown that the Ras-transfected cells are resistant to PDT treatment with ALA and other photosensitisers. Non-treated HB4a cells showed the presence of a thick cortical actin, and stress fibers are mainly organised in the cell periphery, whereas Ras-transfected cells showed actin microspikes, together with an inner actin meshwork. After 24 h of exposure to ALA-PDT with light doses producing 50% of cell death, it was observed on HB4a cells the formation of Ras-like actin microspikes with a reduction of the thickness of the cortical rim, and on Hb4a-Ras, actin surface blebbing appeared replacing the initial spike pattern. E-Cadherin distribution was not changed by the treatment in the surviving cells. These data  suggest  that  in  the  present  model, ALA-PDT  affects the  actin cytoskeleton of both normal and tumour cells independently on their resistance but it does not affect cell to cell adhesion