Effects of ALA-mediated photodynamic therapy on the invasiveness of human glioma cells.
OBJECTIVE
High-grade gliomas are characterized by rapid proliferation, angiogenesis, and invasive growth. Eradication or inhibition of infiltrating glioma cells poses a significant clinical challenge that is unlikely to be solved using conventional treatment regimens consisting of ionizing radiation and chemotherapeutic agents. In this study, we evaluated the effects of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on the invasiveness of human glioma cells migrating from implanted multicell human tumor spheroids.


METHODS
Tumor spheroids, derived from the human glioma cell line ACBT, were implanted into a gel matrix of collagen type I. Twenty-four hours following implantation there was a significant invasion into the surrounding gel by individual tumor cells to an average distance of 400 microm. The cultures were incubated in ALA for 4 hours and then exposed to 635 nm laser light in a titration of fluence level, fluence rate, and drug concentration.


RESULTS
ALA-PDT at a light fluence of 6 J/cm(2) was sufficient to inhibit gloma cell migration distance by 80-90% compared to control cultures, but did not prevent spheroid growth nor was it cytotoxic to the migrating cells. The viability of the migrating cells both in control and PDT-treated cultures receiving 6 J/cm(2) was high, 85 and 65%, respectively. ALA-PDT at fluences of 25 J/cm(2) was clearly cytotoxic for both the infiltrating cells as well as the spheroids. Low fluence rates were more effective at inhibiting tumor cell infiltration than higher ones for a given total fluence.


CONCLUSIONS
Measurement of cell survival, and results from cultures with blocked cell proliferation, indicated a direct migratory inhibition effect on the invading cells rather than cytotoxicity as the most likely mechanism for the inhibition of invasiveness observed following ALA-mediated PDT.
Hirschberg
Henry
H
Beckman Laser Institute, University of California, Irvine, California, USA. hhirschb@uci.edu
Sun
Chung-Ho
CH
Krasieva
Tatiana
T
Madsen
Steen J
SJ
D000622:Aminolevulinic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002468:Cell Physiological Phenomena / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018874:Spheroids, Cellular / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid