Cell-type dependent response to photodynamic treatment in 3D collagen cell cultures

- Cell response to ALA-PDT was cell-type dependent in cell monolayers and 3D collagen cultures.
- ALA-PDT effect evaluated by WST-1 assay did not correlate with modified colony assay in Het-1A cells.
- ALA-PDT killed Kyse 450, but not Kyse 70 or Het-1A cells in 3D collagen gels, if analyzed 24 h after PDT.
- ALA induced PpIX fluorescence was detected in 3D collagen gels of Kyse 450, not Kyse 70 or Het-1A cells.

Photodynamic therapy (PDT) can induce direct tumor cell destruction, indirect tumor cell inactivation due to vascular occlusion as well as immune response. Evidence suggests that the PDT-induced cell death is dependent on both PDT protocol-related as well as microenvironmental factors, and its mode is also decisive for the type of immune response. This suggests potential interrelationship among PDT-induced tumor cell destruction, immune response and microenvironmental factors. In the present study we analyzed the effect of a microenvironmental factor - extracellular matrix on the cellular response to photodynamic treatment in vitro. By using conventional proliferation and modified cell survival assays as well as fluorescence imaging, we compared efficacy of aminolevulinic acid (ALA)-PDT to inactivate three esophageal cell lines in two- and three-dimensional formats. Modified cell colony assay indicated comparable PDT doses leading to death of both Kyse 450 and Het-1A cells on plastic, whereas Kyse 70 cells were only partially responsive. In 3D collagen matrices, we were able to induce only death of Kyse 450 cells by ALA-PDT, if analyzed 24 h after treatment. Consistently, only Kyse 450 cells were able to produce detectable amounts of PpIX after incubation of their 3D collagen cultures with ALA. Our results demonstrate that cellular response to ALA-PDT is cell-type dependent both in two- and three-dimensional formats and indicate that the extracellular matrix might modify it.