Department of Urology, Lanzhou University Second Hospital, Laboratory of Gansu Province for Urological Diseases, Gansu Nephro-Urological Clinical Center, Lanzhou University, Lanzhou, Gansu Province, China.
Department of Pathology, The Second People's Hospital of Gansu Province, Lanzhou, Gansu Province, China.
Int Immunopharmacol. 2024 Feb 15;128:111323. doi: 10.1016/j.intimp.2023.111323. Epub 2024 Jan 28.
This study aims at revealing the relationship between S100A11 and cancer-associated fibroblasts (CAFs) in prostate cancer and improving T cell infiltration into solid tumors.
H&E, IHC and Sirius red staining were used to detect the stroma content in prostate cancer tissues. Stable S100A11 knockdown cell lines DU 145, 22Rv1, RM-1 and NOR-10 were established by lentivirus transfection. Co-culture system of RM-1 and CAFs was established. CCK-8, wound healing and transwell were proceeded to determine proliferation, migration and invasion of prostate cancer cells. Stably knocked-down RM-1 and CAFs were co-injected into C57BL/6 mice to detect the role of S100A11 in vivo. CAFs, CD4 T cell and CD8 T cell in these tumors were assessed by IF. T cell profile was analyzed by flow cytometry.
A significant amount of stroma exists in prostate cancer tissues. Downregulation of S100A11 inhibits proliferation, migration and invasion of human prostate cancer cells in vitro, and suppresses the expression of cancer-associated fibroblasts (CAFs) in vivo. Knockdown of S100A11 enhances the inhibitory effect of Erdafitinib on CAFs in both the co-culture system and in vivo. The combined knockdown of S100A11 in tumor cells and CAFs shows a superior therapeutic effect compared to the individual knockdown in tumor cells alone. Knockdown of S100A11, both in RM-1 and CAFs, combined with Erdafitinib treatment reduces tumorigenicity by suppressing the content of CAFs and increasing the infiltration of CD4 T cell and effective CD8 T cell in tumor.
Downregulation of S100A11 plays a crucial role in enhancing the therapeutic response to Erdafitinib and reversing immunosuppressive tumor microenvironment.
本研究旨在揭示 S100A11 与前列腺癌中的癌症相关成纤维细胞（CAFs）之间的关系，并改善 T 细胞浸润实体瘤。
使用 H&E、免疫组化和天狼猩红染色来检测前列腺癌组织中的基质含量。通过慢病毒转染建立了稳定的 S100A11 敲低细胞系 DU 145、22Rv1、RM-1 和 NOR-10。建立了 RM-1 和 CAFs 的共培养系统。通过 CCK-8、划痕愈合和 Transwell 实验检测前列腺癌细胞的增殖、迁移和侵袭。将稳定敲低的 RM-1 和 CAFs 共同注射到 C57BL/6 小鼠中，以检测 S100A11 在体内的作用。通过免疫荧光（IF）检测这些肿瘤中的 CAFs、CD4 T 细胞和 CD8 T 细胞。通过流式细胞术分析 T 细胞谱。
在前列腺癌组织中存在大量的基质。S100A11 的下调抑制了人前列腺癌细胞的体外增殖、迁移和侵袭，并抑制了体内癌症相关成纤维细胞（CAFs）的表达。在共培养系统和体内，S100A11 的敲低增强了 Erdafitinib 对 CAFs 的抑制作用。与单独敲低肿瘤细胞相比，肿瘤细胞和 CAFs 中同时敲低 S100A11 显示出更好的治疗效果。RM-1 和 CAFs 中 S100A11 的敲低与 Erdafitinib 联合治疗可通过抑制 CAFs 的含量和增加肿瘤中 CD4 T 细胞和有效 CD8 T 细胞的浸润来降低肿瘤发生能力。
S100A11 的下调在增强对 Erdafitinib 的治疗反应和逆转免疫抑制性肿瘤微环境方面发挥着关键作用。
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