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JOURNAL ARTICLE

Vascular-targeted low dose photodynamic therapy stabilizes tumor vessels by modulating pericyte contractility

Sabrina Cavin, Tina Riedel, Petra Rosskopfova, Michel Gonzalez, Greg Baldini, Matthieu Zellweger, Georges Wagnières, Paul J Dyson, Hans-Beat Ris, Thorsten Krueger, Jean Y Perentes
Lasers in Surgery and Medicine 2019 February 19
30779366
Vascular-targeted low-dose photodynamic therapy (L-PDT) was shown to improve chemotherapy distribution in malignant pleural tumors such as malignant pleural mesothelioma (MPM). However, the mechanisms triggered by L-PDT on the tumor vasculature are still debated. In pericyte and endothelial cell co-cultures, we show that pericytes exhibit enhanced sensitivity towards L-PDT compared to endothelial cells, displaying actin stress fibers and cellular contraction via Rho/ROCK kinase signaling myosin light chain and focal adhesion kinase phosphorylation (MLC-P, FAK-P). We then confirm, in two separate MPM models, in mice the phosphorylation of the MLC in pericytes specifically following L-PDT. Furthermore, while L-PDT does not affect tumor vascular density or diameter, we show that it enhances tumor vascular pericyte coverage, leads to a drop in tumor interstitial fluid pressure and enhances the transport of FITC-dextran throughout tumors. In conclusion, L-PDT has the potential to stabilize the tumor vascular bed which improves vascular transport. The mechanism described in the present study may help translate and optimize this approach in patients. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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