Effects of photodynamic therapy on glioma spheroids

Abstract

The present study describes the sensitivity of glioma cells to a haematoporphyrin derivative (Photosan-3) under laser activation (argon-pumped dye laser). The effects of photodynamic therapy (PDT) on cell growth, directional migration and cell invasion were investigated on two human glioma cell lines (GaMg and U-251 Mg). The directional cell migration and spheroid growth was determined for both cell lines exposed to increasing laser energy output (15-35J/cm2) with concentrations of 5 and 7 micrograms/ml of Photosan-3. Both cell lines showed a dose-dependent migratory response to increasing laser irradiation, that was more prominent in the 7 micrograms/ml treatment group. This effect occurred during the first 4 days after drug exposure. Also, spheroids from both cell lines showed a drug and laser output energy dose-dependent inhibition of growth which became apparent after a lag period of 6 days. The lag period was characterized by a decreased growth rate as compared with the control group. During this period the outer cell layers of the spheroids fell apart. The remaining spheroid tissue was not able to migrate and to regrow when exposed to the highest laser energy outputs (30-35J/cm2, 5 and 7 micrograms/ml Photosan-3). These spheroids showed, however, the ability for invasion when confronted with normal brain cell aggregated in vivo. Light microscopic observations of co-cultures between tumour tissue and brain cell aggregates revealed a normal tumour morphology. This indicates that the remaining tumour cells were not dead and could be stimulated to invade the normal tissue when exposed to a normal brain microenvironment.

The use of photodynamic therapy in medical practice

“…Type I reactions involve a direct interaction between the photoexcited dye and cellular oxygen resulting in the production of ROS. However, in Type II reactions, singlet oxygen ( 1 O 2 ) is formed as a result of energy transfer between the photoexcited PS and oxygen ( 100 , 101 ). Both types of reactions can occur simultaneously, and which one prevails depends, among others, on the type, dose and physicochemical properties of the PS used ( 102 ).…”

Understanding the glioblastoma tumor biology to optimize photodynamic therapy: From molecular to cellular events

“…normal cerebral tissue markedly increases GBM cell invasion in nude mice, and that glioma cell invasion correlates with activation of a disintegrin metalloprotease domain 17 (ADAM17)-EGFR-PI3K-Akt pathway(Zhenga et al, 2008). Furthermore, PDT decreased the glioma spheroids cell migration and growth capacity, but these spheroids showed the ability for invasion when confronted with normal brain cells aggregated in vivo(Terzis et al, 1997).Peritumoral edema of glioma tumors is characteristic during the invasive growth and recurrence of glioma. The gene products generated from the cerebral edema promote the transport of tumor cells, water, macromolecules, and plasma through the basement membranes of vessel walls to the peritumoral region.…”

Protein and phosphoprotein levels in glioma and adenocarcinoma cell lines grown in normoxia and hypoxia in monolayer and three-dimensional cultures

“…This observation has led to greater study of tumors in 3D, as it is closer to in situ growth [8-11] even though it lacks many of the supporting extracellular systems (e.g., endothelial cells and capillaries, supporting matrices, cytokines, etc.). In addition, it has been observed that cancer cell lines grown in 2D and 3D culture respond differently to radiation and cytotoxic drugs [12-14]. Why do cell lines exhibit this differential behavior?…”