Supported by NCI grant P01CA55791 and RPCI Support Grant P30CA16056.
Cell-type Selective Phototoxicity Achieved with Chlorophyll-a Derived Photosensitizers in a Co-culture System of Primary Human Tumor and Normal Lung Cells
Article first published online: 3 OCT 2011
© 2011 Wiley Periodicals, Inc.
Photochemistry and Photobiology
Volume 87, Issue 6, pages 1405–1418, November/December 2011
How to Cite
Tracy, E. C., Bowman, M. J., Pandey, R. K., Henderson, B. W. and Baumann, H. (2011), Cell-type Selective Phototoxicity Achieved with Chlorophyll-a Derived Photosensitizers in a Co-culture System of Primary Human Tumor and Normal Lung Cells. Photochemistry and Photobiology, 87: 1405–1418. doi: 10.1111/j.1751-1097.2011.00992.x
- Issue published online: 21 OCT 2011
- Article first published online: 3 OCT 2011
- Accepted manuscript online: 28 AUG 2011 08:57PM EST
- Received 21 June 2011, accepted 19 August 2011
The ATP-dependent transporter ABCG2 exports certain photosensitizers (PS) from cells, implying that the enhanced expression of ABCG2 by cancer cells may confer resistance to photodynamic therapy (PDT) mediated by those PS. In 35 patient-derived primary cultures of lung epithelial and stromal cells, PS with different subcellular localization and affinity for ABCG2 displayed cell-type specific retention both independent and dependent on ABCG2. In the majority of cases, the ABCG2 substrate 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) was lost from fibroblastic cells more rapidly than from their epithelial counterparts, even in the absence of detectable ABCG2 expression, facilitating selective eradication by PDT of epithelial over fibroblastic cells in tumor/stroma co-cultures. Pairwise comparison of normal and transformed epithelial cells also identified tumor cells with elevated or reduced retention of HPPH, depending on ABCG2. Enhanced ABCG2 expression led to the selective PDT survival of tumor cells in tumor/stroma co-cultures. This survival pattern was reversible through HPPH derivatives that are not ABCG2 substrates or the ABCG2 inhibitor imatinib mesylate. PS retention, not differences in subcellular distribution or cell signaling responses, was determining cell type selective death by PDT. These data suggest that up-front knowledge of tumor characteristics, specifically ABCG2 status, could be helpful in individualized PDT treatment design.