Vascular-targeted low dose photodynamic therapy stabilizes tumor vessels by modulating pericyte contractility
Vascular-targeted low dose photodynamic therapy stabilizes tumor vessels by modulating pericyte contractility
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DOI：
10.1002/lsm.23069
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发表时间：
2019-08-01
影响因子：
2.4
通讯作者：
Perentes, Jean Y.
中科院分区：
文献类型：
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作者：
Cavin, Sabrina;Riedel, Tina;Perentes, Jean Y.
血管靶向低剂量光动力疗法（L-PDT）被证明可以改善恶性胸膜肿瘤（例如恶性胸膜间皮瘤（MPM））的化疗分布。然而，L-PDT 对肿瘤血管系统触发的机制仍存在争议。在周细胞和内皮细胞共培养中，我们发现与内皮细胞相比，周细胞对 L-PDT 表现出增强的敏感性，通过 Rho/ROCK 激酶信号传导肌球蛋白轻链和粘着斑激酶磷酸化（MLC-P、FAK-P）显示肌动蛋白应力纤维和细胞收缩。然后，我们在两个独立的 MPM 模型中确认小鼠周细胞中 MLC 的磷酸化，特别是在 L-PDT 之后。此外，虽然L-PDT不影响肿瘤血管密度或直径，但我们发现它增强了肿瘤血管周细胞覆盖，导致肿瘤间质液压力下降并增强了FITC-葡聚糖在整个肿瘤中的转运。总之，L-PDT 具有稳定肿瘤血管床的潜力，从而改善血管运输。本研究中描述的机制可能有助于在患者中转化和优化这种方法。激光外科。医学。 51:550-561，2019 年。(c) 2019 Wiley 期刊公司。
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. (c) 2019 Wiley Periodicals, Inc.