Photo‐destruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Co‐culture Models,Photochemistry and Photobiology

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Photo‐destruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Co‐culture Models
Photochemistry and Photobiology ( IF 2.6 ) Pub Date : 2020-10-27 , DOI: 10.1111/php.13339
Vida Karimnia ₁ , Imran Rizvi _{2,

3,

4} , Frank J Slack ₅ , Jonathan P Celli ₁

Affiliation

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. The dismal response of PDAC to virtually all therapeutics is associated, in part, with a characteristically dense fibrotic stroma. This stroma acts not only as a barrier to drug perfusion, but also promotes tumor survival through paracrine crosstalk and biophysical interactions. Photodynamic therapy (PDT) is being explored for PDAC treatment, though the impact of tumor-promoting stromal crosstalk on PDT response in PDAC is not well characterized. The current study assesses the effect of tumor-stroma interactions on response to PDT or chemotherapy in heterocellular 3D co-cultures using PDAC cells and two different fibroblastic cell types (pancreatic stellate cells, PSCs, and a normal human fibroblast cell line, MRC5) embedded in extracellular matrix (ECM). While stromal fibroblasts promote resistance to chemotherapy as expected, PDAC 3D nodules in co-culture with fibroblasts exhibit increased response to PDT relative to homotypic cultures. These results point to the potential for PDT to overcome tumor-promoting stromal interactions associated with poor therapeutic response in PDAC.

中文翻译：

基质成纤维细胞的光破坏增强 3D 胰腺癌共培养模型中肿瘤对 PDT 的反应

胰腺导管腺癌（PDAC）是最致命的人类癌症之一。PDAC 对几乎所有治疗方法的不良反应部分与特征性致密纤维化基质有关。这种基质不仅充当药物灌注的屏障，而且还通过旁分泌串扰和生物物理相互作用促进肿瘤存活。光动力疗法 (PDT) 正在探索用于 PDAC 治疗，但促肿瘤基质串扰对 PDAC 中 PDT 反应的影响尚未得到很好的表征。目前的研究使用 PDAC 细胞和两种不同的成纤维细胞类型（胰腺星状细胞，PSC 和正常人成纤维细胞系，MRC5）嵌入异质细胞 3D 共培养物中，评估肿瘤-基质相互作用对 PDT 或化疗反应的影响存在于细胞外基质（ECM）中。虽然基质成纤维细胞如预期的那样促进对化疗的抵抗，但与同型培养物相比，与成纤维细胞共培养的 PDAC 3D 结节表现出对 PDT 的反应增强。这些结果表明 PDT 有可能克服与 PDAC 治疗反应不佳相关的促肿瘤基质相互作用。

更新日期：2020-10-27

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