Format

Send to

Choose Destination
Lasers Surg Med. 2019 Aug;51(6):550-561. doi: 10.1002/lsm.23069. Epub 2019 Feb 19.

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

Author information

1
Department of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
2
Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
3
Institute of Physics, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.

Abstract

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. 51:550-561, 2019.

KEYWORDS:

RhoA; focal adhesion kinase; malignant pleural mesothelioma; myosin light chain; pericyte activation; photodynamic therapy; vascular remodeling

PMID:
30779366
DOI:
10.1002/lsm.23069

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center