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光动力疗法对着色性干皮病和基底细胞痣综合征患者皮肤成纤维细胞的影响。

Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients.

作者信息

Zamarrón Alicia, García Marta, Río Marcela Del, Larcher Fernando, Juarranz Ángeles

机构信息

Department of Biology, Faculty of Sciences, Autónoma University of Madrid, IRYCIS, Madrid, Spain.

Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain.

出版信息

Oncotarget. 2017 Aug 24;8(44):77385-77399. doi: 10.18632/oncotarget.20485. eCollection 2017 Sep 29.

DOI:10.18632/oncotarget.20485
PMID:29100394
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5652786/
Abstract

PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role.

摘要

光动力疗法（PDT）被广泛应用于治疗非黑色素瘤皮肤癌的癌前病变和恶性病变（光化性角化病、基底细胞癌和鳞状细胞癌）。在光动力疗法（PDT）中，光敏剂（PS）、光和氧的相互作用会导致活性氧（ROS）的形成，从而选择性地根除肿瘤细胞。着色性干皮病（XP）和基底细胞痣综合征（GS）患者在阳光暴露部位患皮肤癌的风险很高。因此，将PDT用作预防性治疗可能对这些综合征构成一种非常有前景的治疗方式。鉴于癌症相关成纤维细胞（CAF）在肿瘤进展中的已证实作用以及一些易患癌症的遗传性皮肤病成纤维细胞的假定CAF特征，在本研究中，我们进一步表征了XP和GS真皮成纤维细胞的表型，并评估了它们与从健康供体获得的真皮成纤维细胞相比对甲基-δ-氨基乙酰丙酸（MAL）-PDT的反应。我们在此表明，XP/GS成纤维细胞表现出明显的CAF特征，并且即使在受到紫外线刺激后，对PDT的反应也明显更高，这突出了这种治疗方法对这些罕见皮肤病况的价值，并且可能对CAF起主要作用的其他形式的皮肤癌也有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/66bb7771f046/oncotarget-08-77385-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/60d248a08733/oncotarget-08-77385-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/e4848732b021/oncotarget-08-77385-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/d1810f6f1a5d/oncotarget-08-77385-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/4d49e4d0ebff/oncotarget-08-77385-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/02081079da96/oncotarget-08-77385-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/13a553e21b77/oncotarget-08-77385-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/66bb7771f046/oncotarget-08-77385-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/60d248a08733/oncotarget-08-77385-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/e4848732b021/oncotarget-08-77385-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/d1810f6f1a5d/oncotarget-08-77385-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/4d49e4d0ebff/oncotarget-08-77385-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/02081079da96/oncotarget-08-77385-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/13a553e21b77/oncotarget-08-77385-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/437d/5652786/66bb7771f046/oncotarget-08-77385-g007.jpg

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