文章：

CXCR1在MDA-PCa-2b细胞中的表达通过上调ITM2A抑制肿瘤生长

CXCR1 Expression in MDA-PCa-2b Cell Upregulates ITM2A to Inhibit Tumor Growth

原文发布日期：11 December 2024

DOI: 10.3390/cancers16244138

类型: Article

开放获取: 是

英文摘要：

Background: Chemokines, along with their receptors, exert critical roles in tumor development and progression. In prostate cancer (PCa), interleukin-8 (IL-8/CXCL8) was shown to enhance angiogenesis, proliferation, and metastasis. CXCL8 activates two receptors, CXCR1 and CXCR2. While CXCR2 expression was shown to promote PCa growth and metastasis, the role of CXCR1 remains unclear. Methods: In this study, we stably expressed CXCR1 and, as control, CXCR2 in the androgen-dependent PCa cell line MDA-PCa-2b to evaluate the effect of CXCR1 in tumor development. Results: MDA-PCa-2b-CXCR1 cells showed decreased cell migration, protein kinase-B (AKT) activation, prostate-specific antigen (PSA) expression, cell proliferation, and tumor development in nude mice, relative to MDA-PCa-2b-Vec and MDA-PCa-2b-CXCR2 cells. MDA-PCa-2b-CXCR1 cells also displayed a significant transition to mesenchymal phenotypes as characterized by decreased E-cadherin expression and a corresponding increased level of N-cadherin and vimentin expression. RNA-seq and Western blot analysis revealed a significant increase in the tumor suppressor integral membrane protein 2A (ITM2A) expression in MDA-PCa-2b-CXCR1 compared to control cells. In prostate adenocarcinoma tissue, ITM2A expression was also shown to be downregulated relative to a normal prostate. Interestingly, the overexpression of ITM2A in MDA-PCa-2b cells (MDA-PCa-2b-ITM2A-GFP) inhibited tumor growth similar to that of MDA-PCa-2b-CXCR1. Conclusions: Taken together, the data suggest that CXCR1 expression in MDA-PCa-2b cells may upregulate ITM2A to abrogate tumor development.

摘要翻译： 

背景：趋化因子及其受体在肿瘤发生发展中发挥关键作用。在前列腺癌中，白细胞介素-8（IL-8/CXCL8）被证实可促进血管生成、增殖和转移。CXCL8通过激活CXCR1和CXCR2两种受体发挥作用。虽然CXCR2表达已被证明可促进前列腺癌生长和转移，但CXCR1的作用尚不明确。方法：本研究在雄激素依赖性前列腺癌细胞系MDA-PCa-2b中稳定表达CXCR1，并以CXCR2作为对照，以评估CXCR1在肿瘤发展中的作用。结果：与MDA-PCa-2b-Vec和MDA-PCa-2b-CXCR2细胞相比，MDA-PCa-2b-CXCR1细胞表现出细胞迁移能力下降、蛋白激酶B（AKT）活化减弱、前列腺特异性抗原（PSA）表达降低、细胞增殖减缓，以及在裸鼠体内肿瘤生长受抑制。MDA-PCa-2b-CXCR1细胞还表现出显著的间质表型转化特征，具体表现为E-钙黏蛋白表达下降，同时N-钙黏蛋白和波形蛋白表达水平相应升高。RNA测序和蛋白质印迹分析显示，与对照组细胞相比，MDA-PCa-2b-CXCR1细胞中肿瘤抑制整合膜蛋白2A（ITM2A）表达显著增加。在前列腺腺癌组织中，ITM2A表达也较正常前列腺组织下调。值得注意的是，在MDA-PCa-2b细胞中过表达ITM2A（MDA-PCa-2b-ITM2A-GFP）可抑制肿瘤生长，其效果与MDA-PCa-2b-CXCR1细胞相似。结论：综合以上数据表明，MDA-PCa-2b细胞中CXCR1的表达可能通过上调ITM2A来抑制肿瘤发展。

原文链接：

CXCR1 Expression in MDA-PCa-2b Cell Upregulates ITM2A to Inhibit Tumor Growth