C-X-C 基序趋化因子配体 13 在氨基酮戊酸光动力疗法治疗皮肤鳞状细胞癌中的作用。
The effect of C-X-C motif chemokine ligand 13 in cutaneous squamous cell carcinoma treated with aminolevulinic acid-photodynamic therapy.
机构信息
Department of Dermatology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
出版信息
Photodiagnosis Photodyn Ther. 2019 Jun;26:389-394. doi: 10.1016/j.pdpdt.2019.04.018. Epub 2019 Apr 22.
BACKGROUND
Active recruitment of inflammatory cells into tumors may be vital for antitumor immunity in cutaneous squamous cell carcinoma (cSCC) after photodynamic therapy. Chemokines play important roles in inflammatory cell recruitment. Moreover, C-X-C motif chemokine ligand 13 (CXCL13) is thought to be a pivotal chemokine involved in inflammatory response and antitumor effect. Here, we examined the roles of CXCL13 in the response of cSCC to ALA-PDT.
METHODS
Microarray analysis was used to select the chemokines involved in cSCC treated with ALA-PDT. The expression and transcriptional activity of CXCL13 were assessed by immunohistochemistry and quantitative real-time polymerase chain reaction. Western blotting was used to detect C-X-C motif chemokine receptor 5 (CXCR5) expression. The role of CXCL13 in ALA-PDT efficacy was assessed in vivo.
RESULTS
Microarray analysis of total 63 chemokines and their receptors showed that the expression of 21 chemokines and 13 receptors were up-regulated in cSCC after ALA-PDT; in particular, CXCL13 was significantly upregulated. Immunohistochemistry showed that cancer-associated fibroblasts (CAFs) may be the main source of CXCL13 upregulation in the cSCC microenvironment after ALA-PDT. The efficacy of ALA-PDT in the treatment of cSCC was significantly reduced after CXCL13 inhibition.
CONCLUSION
CXCL13 plays important roles in the antitumor effect of ALA-PDT for cSCC and may originate mainly from CAFs in the cSCC microenvironment.
背景
光动力疗法（PDT）后，炎性细胞向肿瘤内的主动募集可能对皮肤鳞状细胞癌（cSCC）的抗肿瘤免疫至关重要。趋化因子在炎性细胞募集中发挥重要作用。此外，C-X-C 基序趋化因子配体 13（CXCL13）被认为是参与炎症反应和抗肿瘤作用的关键趋化因子。在此，我们研究了 CXCL13 在 cSCC 对 ALA-PDT 反应中的作用。
方法
采用微阵列分析选择经 ALA-PDT 处理的 cSCC 涉及的趋化因子。通过免疫组织化学和实时定量聚合酶链反应评估 CXCL13 的表达和转录活性。采用 Western blot 检测 C-X-C 基序趋化因子受体 5（CXCR5）的表达。在体内评估 CXCL13 在 ALA-PDT 疗效中的作用。
结果
对 63 种趋化因子及其受体的全基因组分析显示，ALA-PDT 后 cSCC 中 21 种趋化因子和 13 种受体的表达上调，尤其是 CXCL13 显著上调。免疫组织化学显示，在 ALA-PDT 后 cSCC 微环境中，癌症相关成纤维细胞（CAFs）可能是 CXCL13 上调的主要来源。在治疗 cSCC 时，ALA-PDT 的疗效在 CXCL13 抑制后明显降低。
结论
CXCL13 在 ALA-PDT 治疗 cSCC 的抗肿瘤作用中发挥重要作用，可能主要来源于 cSCC 微环境中的 CAFs。
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