Abstract
Photodynamic therapy (PDT) involves the administration of a photosensitizer followed by local illumination of a tumor with light of the appropriate wavelength to activate a specific drug. Efficacy is high for small superficial tumors and, except for temporary skin photosensitization, there are no long-term side effects if appropriate protocols are followed. However, an inherent consequence of PDT is local hypoxia. Hypoxia is the major stimulus for vascular endothelial growth factor (VEGF) production and secretion. VEGF could contribute to tumor survival and regrowth and therefore could be one of the factors impairing PDT from achieving its full tumoricidal potential. Therefore, an understanding of tumor cell responses to PDT will help in the design of new interventions and potentially improve long-term survival of PDT treated patients. It is well known that the cells in tumor tissue are heterogeneous in terms of morphology and differentiation status, even if the tumor consists of progeny developed from a single neoplastic cell. In this study, we found that morphologically heterogeneous tumor cell clones had differing photosensitizer (talaporfin sodium) uptake and PDT sensitivity. Morphologically heterogeneous clones were formed from a cultured cell line (KYSE70) established from a single human esophageal carcinoma tissue. Five subclones were separated from a single clone of KYSE70 cells. Three subclones were mainly flat and diffusive, while the other two formed mounds. Some subclones were more PDT-sensitive than the other subclones, although the intracellular uptake of talaporfin sodium was lower. Although talaporfin sodium could be effectively taken up by some subclones, these subclones were not effectively PDT sensitive, irrespective of cell morphology. The data demonstrated that a single tumor cell has the potential to produce progeny that are heterogeneous in terms of morphology and PDT sensitivity, irrespective of intracellular talaporfin sodium concentration. Further improvements in the clinical application of PDT for heterogeneous tumor cells are expected, since PDT may be ultimately useful as a clinical tumor therapy.
