CXCR1在MDA-PCa-2b细胞中的表达上调ITM2A以抑制肿瘤生长。

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

作者信息

Adekoya Timothy O, Smith Nikia, Kothari Parag, Dacanay Monique A, Li Yahui, Richardson Ricardo M

机构信息

Cancer Research Program, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, Durham, NC 27707, USA.

Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA.

出版信息

Cancers (Basel). 2024 Dec 11;16(24):4138. doi: 10.3390/cancers16244138.

DOI:10.3390/cancers16244138

PMID:39766038

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11674668/

Abstract

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

背景

趋化因子及其受体在肿瘤的发生和发展过程中发挥着关键作用。在前列腺癌（PCa）中，白细胞介素-8（IL-8/CXCL8）可促进血管生成、细胞增殖和转移。CXCL8可激活两种受体，即CXCR1和CXCR2。虽然CXCR2的表达已被证明可促进PCa的生长和转移，但CXCR1的作用仍不清楚。

方法

在本研究中，我们在雄激素依赖的PCa细胞系MDA-PCa-2b中稳定表达CXCR1，并以CXCR2作为对照，以评估CXCR1在肿瘤发生中的作用。

结果

与MDA-PCa-2b-Vec和MDA-PCa-2b-CXCR2细胞相比，MDA-PCa-2b-CXCR1细胞在裸鼠体内的细胞迁移、蛋白激酶B（AKT）激活、前列腺特异性抗原（PSA）表达、细胞增殖及肿瘤生长均受到抑制。MDA-PCa-2b-CXCR1细胞还表现出明显的间充质表型转变，其特征为E-钙黏蛋白表达降低，N-钙黏蛋白和波形蛋白表达相应增加。RNA测序和蛋白质印迹分析显示，与对照细胞相比，MDA-PCa-2b-CXCR1中肿瘤抑制因子整合膜蛋白2A（ITM2A）的表达显著增加。在前列腺腺癌组织中，与正常前列腺相比，ITM2A表达也下调。有趣的是，MDA-PCa-2b细胞中ITM2A的过表达（MDA-PCa-2b-ITM2A-GFP）抑制肿瘤生长的作用与MDA-PCa-2b-CXCR1相似。