Reversal of the Migratory and Invasive Phenotype of Ras-Transfected Mammary Cells by Photodynamic Therapy Treatment

Abstract

Photodynamic therapy (PDT) is a non-thermal technique for inducing tumor damage following administration of a light-activated photosensitizing drug (PS). In a previous work we found that PDT induces cytoskeleton changes in HB4a-Ras cells (human mammary breast carcinoma HB4a cells transfected with the RAS oncogene). In the present work we have studied the migratory and invasive features and the expression of proteins related to these processes on HB4a-Ras cells after three successive cycles of PDT using different PSs: 5-aminolevulinic acid (ALA), Verteporfin (Verte), m-tetrahydroxyphenylchlorin (m-THPC), and Merocyanine 540 (MC). A slight (1.25- to 2-fold) degree of resistance was acquired in cell populations subjected to the three successive PDT treatments. However, complete cell killing was achieved after a light dose increase. Regardless of the PS employed, all the PDT-treated populations had shorter stress fibres than the untreated control HB4a-Ras cells, and the number of dorsal stress fibres was decreased in the PDT-treated populations. E-Cadherin distribution, which was already aberrant in HB4a-Ras cells, became even more diffuse in the PDT-treated populations, though its expression was increased in some of them. The strong migratory and invasive ability of HB4a-Ras cells in vitro was impaired in all the PDT-treated populations, with a behavior that was similar to the parental non-tumoral HB4a cells. MMP-2 and -9 metalloproteinase activities were also impaired in the PDT-treated populations. The evidence presented herein suggests that the cells surviving PDT would be less metastatic than the initial population. These findings encourage the use of PDT in combination with other treatments such as intraoperative or post-surgery therapeutic procedures. J. Cell. Biochem. 118: 464-477, 2017. © 2016 Wiley Periodicals, Inc.

Photosensitization of a subcutaneous tumour by the natural anthraquinone parietin and blue light

“…Cell migration of cells surviving PTN-PDT was determined employing a wound-healing assay 28 . The LM2 cells were seeded in 6-multiwell plates and allowed to grow until confluency, and afterwards, they were treated with PTN-PDT as indicated above.…”

Photodynamic therapy with verteporfin accelerates apoptotic bleb formation in human ameloblastoma

“…Although the maximum concentration of VP in the previous study was 2.0 μg/mL (Calvo et al, 2017), there were two studies that applied 1.0 μg/mL (Akens et al, 2014;Glidden et al, 2012). Because the lowest but effective concentration of VP must be determined, we conducted experiments at 0.01, 0.1, and 1.0 μg/mL in this study.…”

“…The VP dose concentration and laser irradiation conditions were determined with reference to previous literature (Akens et al, 2014;Calvo et al, 2017;Celli et al, 2011;Mae et al, 2020), as shown in Table 1.…”

The Photosensitizer Temoporfin (mTHPC) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade†‡

“…on microtubules and cell endosomal transport (181). Other recent publications found phenotype shifts in macrophages elicited by temoporfin nanoparticles (163) and in Ras‐transfected mammary cells, where a reduction of the migratory and invasive ability was observed for cells treated with PDT using different photosensitizers including temoporfin (162). Sphingolipids and their ceramide subgroup are building blocks of membranes, but also fulfil numerous other functions in the cell and have been shown to be involved in PDT (95,169).…”