癌症相关成纤维细胞衍生的外泌体PIK3AP1促进前列腺癌细胞的恶性进展和免疫逃逸

IF 3.2 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-09-04 DOI:10.1016/j.prp.2025.156209

Tan Li , Cheng Yi , Zhendong Xiang, Xiangyun You, Junfeng Yu

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引用次数: 0

摘要

前列腺癌是一种常见的恶性肿瘤。癌症相关成纤维细胞（Cancer-associated fibroblasts, CAFs）在肿瘤的发生发展中起着重要作用。b细胞适配蛋白（PIK3AP1）与细胞生长、抑制细胞凋亡和肿瘤治疗有关。因此，本研究旨在探讨CAFs外泌体和PIK3AP1在PCa中的作用和机制。方法采用形态学观察和western blot方法对正常成纤维细胞（nf）、CAFs和外泌体进行鉴定。分别通过5-乙基-2 ' -脱氧尿苷（EdU）、transwell和细胞计数试剂盒-8 （CCK8）检测增殖、迁移、侵袭和细胞活力。流式细胞术检测CD8+T细胞的增殖和凋亡情况。采用qRT-PCR和western blot分析基因表达。利用动物实验分析了cafa衍生外泌体PIK3AP1在体内的作用。结果scaf来源的外泌体促进前列腺癌细胞增殖、迁移、侵袭、细胞活力和免疫逃逸。PIK3AP1在CAFs和PCa细胞中表达上调，与肿瘤免疫逃逸有关。在体内和体外，PIK3AP1促进了PCa的恶性行为和免疫逃逸。cafs衍生的外泌体通过携带PIK3AP1促进PCa的进展和免疫逃逸。结论scaf来源的外泌体通过PIK3AP1促进前列腺癌细胞的恶性行为和免疫逃逸。

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Cancer-associated fibroblasts-derived exosome PIK3AP1 promotes the malignant progression and immune escape of prostate cancer cells

Background

Prostate cancer (PCa) is a common malignant cancer. Cancer-associated fibroblasts (CAFs) play an important role in occurrence and development of tumors. B-cell adapter protein (PIK3AP1) is related to cell growth, inhibits cell apoptosis and mediates tumor therapy. Thereby, this study aims to explore the role and mechanism of CAFs exosomes and PIK3AP1 in PCa.

Methods

Normal fibroblasts (NFs), CAFs, and exosomes were characterized by morphology observation and western blot. The proliferation, migration, invasion, and cell viability were examined by 5-Ethynyl-2’-deoxyuridine (EdU), transwell, and cell counting kit-8 (CCK8) assays, respectively. Proliferation and apoptosis of CD8⁺T cells were tested using flow cytometry. Gene expression was analyzed using qRT-PCR and western blot. Animal experiments were utilized to analyze the role of CAF-derived exosome PIK3AP1 in vivo.

Results

CAFs-derived exosomes promoted the PCa cell proliferation, migration, invasion, cell viability, and immune escape. PIK3AP1 was up-regulated in CAFs and PCa cells and related to tumor immune escape. PIK3AP1 facilitated the malignant behavior of PCa and the immune escape in vivo and in vitro. CAFs-derived exosome promoted PCa progression and immune escape via carrying PIK3AP1.

Conclusions

CAFs-derived exosomes promote the malignant behavior and immune escape of PCa cells by PIK3AP1.

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.