Putative role of heparan sulfate proteoglycan expression and shedding on the proliferation and survival of cells after photodynamic therapy.
BACKGROUND
Photodynamic therapy is based on the selective retention of a photosensitizer by highly proliferating cells and its activation with light at the appropriate wavelength. This combination generates reactive oxygen species that ultimately kill the cells. Some cells, however, may survive photodynamic therapy and the interaction of these cells with the extracellular matrix has profound effect in tumor biology. The knowledge of photodynamic therapy action on the extracellular matrix has not been fully explored. It has been focused mainly on integrins, matrix metalloproteinases and on growth factors and immunological mediators. Other important molecules involved in the regulation of many cell processes are the glycosaminoglycans, polymers of disaccharide units, present on the cell surface and in the extracellular matrix. In most cases, the glycosaminoglycans occur as proteoglycans.


OBJECTIVE
The purpose of the present investigation is to evaluate heparan sulfate proteoglycan expression and shedding, and its relation to the survival of the remaining cells, after a liposomal-AlClPc based photodynamic treatment.


METHODS
A wild-type endothelial cell derived from rabbit aorta and its counterpart transfected with EJ-ras oncogene were used.


RESULTS
Both cell lines presented augmented heparan sulfate proteoglycan syndecan-4 mRNA expression, augmented synthesis of heparan sulfate chains and increased shedding. Also, the formation of stress fibers on the border of the cells and the arrest in G(1) phase of the cell cycle was observed.


CONCLUSIONS
These results show that surviving cells after photodynamic therapy exhibit changes in their morphology and cell processes that differ from that of non-treated cells, and these changes are probably hindering the cells from resuming normal proliferation.
Pazos
Marcelo de Castro
Mde C
Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Ricci
Ritchelli
R
Simioni
Andreza R
AR
Lopes
Carla C
CC
Tedesco
Antonio C
AC
Nader
Helena B
HB
D000199:Actins / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis* / Q000502:physiology; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053667:Syndecans / Q000235:genetics
D000199:Actins; D019812:Heparan Sulfate Proteoglycans; D017319:Photosensitizing Agents; D012333:RNA, Messenger; D053667:Syndecans