Effects of ALA-mediated photodynamic therapy on the invasiveness of human glioma cells

✍ Scribed by Henry Hirschberg; Chung-Ho Sun; Tatiana Krasieva; Steen J. Madsen

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 151 KB
• Volume: 38
• Category: Article
• ISSN: 0196-8092
• DOI: 10.1002/lsm.20445

✦ Synopsis

Background and 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. Study Design/Materials and 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 mm. 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 PDTtreated 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. Conclusion: 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.