
浏览全部资源
扫码关注微信
400038 重庆,陆军军医大学(第三军医大学)第一附属医院全军普通外科中心,微创胃肠外科中心
[钱锋,E-mail: qianfengpuwaia@163.comQIAN Feng, E-mail: qianfengpuwaia@163.com
收稿:2021-12-15,
修回:2022-02-17,
纸质出版:2022-04-30
移动端阅览
吴彬, 王俊杰, 任志祥, 等. PLXDC2调控丝状伪足形成促进胃癌侵袭转移的机制研究[J]. 陆军军医大学学报, 2022,44(8):774-781.
Bin WU, Junjie WANG, Zhixiang REN, et al. Plexin-domain containing 2 promotes invasion and metastasis of gastric cancer by regulating filopodia formation[J]. Journal of Army Medical University, 2022, 44(8): 774-781.
吴彬, 王俊杰, 任志祥, 等. PLXDC2调控丝状伪足形成促进胃癌侵袭转移的机制研究[J]. 陆军军医大学学报, 2022,44(8):774-781. DOI: 10.16016/j.2097-0927.202112121.
Bin WU, Junjie WANG, Zhixiang REN, et al. Plexin-domain containing 2 promotes invasion and metastasis of gastric cancer by regulating filopodia formation[J]. Journal of Army Medical University, 2022, 44(8): 774-781. DOI: 10.16016/j.2097-0927.202112121.
目的
2
观察PLXDC2(plexin-domain containing 2)对胃癌侵袭转移的作用,并探讨其机制。
方法
2
收集TCGA-STAD数据库中胃癌患者资料,统计分析PLXDC2表达与胃癌临床病理参数及患者预后的关系。构建PLXDC2敲低/过表达胃癌细胞,用Matrigel-transwell侵袭实验和小鼠腹膜转移模型评估PLXDC2对胃癌细胞侵袭转移能力的影响。Western blot、免疫荧光检测PLXDC2在胃癌中发挥作用的潜在机制。
结果
2
PLXDC2在胃癌组织中高表达(
P
<
0.05),表达水平与组织学分级(
P
<
0.01)、TNM分期(
P
<
0.05)和T分期(
P
<
0.05)呈正相关关系,与患者预后呈负相关关系(
P
<
0.05)。Cox回归表明PLXDC2是影响患者预后的独立危险因素(
P
<
0.05)。沉默PLXDC2表达显著抑制胃癌细胞的体外侵袭(
P
<
0.01)和体内转移(
P
<
0.01)能力,而过表达PLXDC2后得到相反的结果。改变PLXDC2的表达相应地改变胃癌细胞中Cdc42的表达和丝状伪足的形成。
结论
2
PLXDC2通过调控丝状伪足的形成促进胃癌细胞的侵袭转移,可作为胃癌潜在的预后标志物和治疗靶点。
Objective
2
To investigate the role of plexin-domain containing 2 (PLXDC2) in regulating the invasion and metastasis of gastric cancer (GC) and explore its mechanism.
Methods
2
The data of GC cases were collected from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) database
and the relationship between PLXDC2 expression and the clinicopathological parameters as well as the prognosis of GC patients were statistically analyzed. PLXDC2 knockdown and overexpression GC cell models were constructed respectively
then Matrigel-transwell invasion assay and mouse peritoneal metastasis model were performed to evaluate the effect of PLXDC2 on the invasion and metastasis of GC cells. Western blotting and immunofluorescence assay were also adopted to investigate the potential mechanism of PLXDC2 in GC.
Results
2
PLXDC2 was highly expressed in GC tissues (
P
<
0.05)
and its expression level was positively correlated with neoplasm histological grade (
P
<
0.01)
TNM stage (
P
<
0.05) and T stage (
P
<
0.05)
while negatively with the prognosis of patients (
P
<
0.05). Cox regression analysis identified PLXDC2 as an independent risk factor for prognosis (
P
<
0.05). Silencing PLXDC2 significantly inhibited the invasion ability of GC cells
in vitro
(
P
<
0.01) and metastasis
in vivo
(
P
<
0.01)
whereas overexpression of PLXDC2 obtained the opposite results. Moreover
the changes of PLXDC2 level correspondingly affected the expression of Cdc42 and the formation of filopodia in GC cells.
Conclusion
2
PLXDC2 promotes the invasion and metastasis of GC cells by regulating the formation of filopodia
and may act as a potential prognostic biomarker and therapeutic target for GC.
SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590.
WONG M C S, HUANG J J, CHAN P S F, et al . Global incidence and mortality of gastric cancer, 1980-2018[J ] . JAMA Netw Open, 2021, 4(7): e2118457. DOI: 10.1001/jamanetworkopen.2021.18457.
郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005.
ZHENG R S, SUN K X, ZHANG S W, et al . Report of cancer epidemiology in China, 2015[J ] . Chin J Oncol, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.005.
RAWLA P, BARSOUK A. Epidemiology of gastric cancer: global trends, risk factors and prevention[J]. Prz Gastroenterol, 2019, 14(1): 26-38. DOI: 10.5114/pg.2018.80001.
HARADA K, LOPEZ A, SHANBHAG N, et al . Recent advances in the management of gastric adenocarcinoma patients[J ] . F1000Research, 2018, 7: 1365. DOI: 10.12688/f1000research.15133.1.
SMYTH E C, NILSSON M, GRABSCH H I, et al . Gastric cancer[J ] . Lancet, 2020, 396(10251): 635-648. DOI: 10.1016/S0140-6736(20)31288-5.
CARSON-WALTER E B, WATKINS D N, NANDA A, et al . Cell surface tumor endothelial markers are conserved in mice and humans[J ] . Cancer Res, 2001, 61(18): 6649-6655.
ST CROIX B, RAGO C, VELCULESCU V, et al . Genes expressed in human tumor endothelium[J ] . Science, 2000, 289(5482): 1197-1202. DOI: 10.1126/science.289.5482.1197.
ATTOFF K, GLIGA A, LUNDQVIST J, et al . Whole genome microarray analysis of neural progenitor C17.2 cells during differentiation and validation of 30 neural mRNA biomarkers for estimation of developmental neurotoxicity[J ] . PLoS One, 2017, 12(12): e0190066.DOI: 10.1371/journal.pone.0190066.
SHANG Z Y, LI C X, LIU X M, et al . PEDF gene deletion disrupts corneal innervation and ocular surface function[J ] . Invest Ophthalmol Vis Sci, 2021, 62(7): 18. DOI: 10.1167/iovs.62.7.18.
DAVIES G, CUNNICK G H, MANSEL R E, et al . Levels of expression of endothelial markers specific to tumour-associated endothelial cells and their correlation with prognosis in patients with breast cancer[J ] . Clin Exp Metastasis, 2004, 21(1): 31-37. DOI: 10.1023/b: clin.0000017168.83616.d0.
YAMAMOTO N, EGUCHI A, HIROKAWA Y, et al . Expression pattern of plexin domain containing 2 in human hepatocellular carcinoma[J ] . Monoclon Antib Immunodiagn Immunother, 2020, 39(2): 57-60. DOI: 10.1089/mab.2019.0050.
LAVORATO-ROCHA A M, AKAGI E M, DE MELO MAIA B, et al . An integrative approach uncovers biomarkers that associate with clinically relevant disease outcomes in vulvar carcinoma[J ] . Mol Cancer Res, 2016, 14(8): 720-729. DOI: 10.1158/1541-7786.MCR-15-0366.
WANG Y J, LI H X. Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics[J]. Oncol Lett, 2018, 15(6): 9793-9801. DOI: 10.3892/ol.2018.8600.
GUAN Y M, DU Y Z, WANG G Z, et al . Overexpression of PLXDC2 in stromal cell-associated M2 macrophages is related to EMT and the progression of gastric cancer[J ] . Front Cell Dev Biol, 2021, 9: 673295. DOI: 10.3389/fcell.2021.673295.
DAVIS S, MELTZER P S. GEOquery: a bridge between the gene expression omnibus (GEO) and BioConductor[J]. Bioinformatics, 2007, 23(14): 1846-1847. DOI: 10.1093/bioinformatics/btm254.
GIBIEŽA P, PETRIKAITĚ V. The regulation of actin dynamics during cell division and malignancy[J]. Am J Cancer Res, 2021, 11(9): 4050-4069.
CASWELL P T, ZECH T. Actin-based cell protrusion in a 3D matrix[J]. Trends Cell Biol, 2018, 28(10): 823-834. DOI: 10.1016/j.tcb.2018.06.003.
FERRARI R, INFANTE E, CHAVRIER P. Nucleus-invadopodia Duo during cancer invasion[J]. Trends Cell Biol, 2019, 29(2): 93-96. DOI: 10.1016/j.tcb.2018.11.006.
EDDY R J, WEIDMANN M D, SHARMA V P, et al . Tumor cell invadopodia: invasive protrusions that orchestrate metastasis[J ] . Trends Cell Biol, 2017, 27(8): 595-607. DOI: 10.1016/j.tcb.2017.03.003.
MALDONADO M, MEDINA J I, VELAZQUEZ L, et al . Targeting rac and Cdc42 GEFs in metastatic cancer[J ] . Front Cell Dev Biol, 2020, 8: 201. DOI: 10.3389/fcell.2020.00201.
ZHANG Q L, LIANG H, ZHAO X Y, et al . PTENε suppresses tumor metastasis through regulation of filopodia formation[J ] . EMBO J, 2021, 40(10): e105806. DOI: 10.15252/embj.2020105806.
KIDANI T, YASUDA R, MIYAWAKI J, et al . Bis phenol A inhibits cell proliferation and reduces the motile potential of murine LM8 osteo sarcoma cells[J ] . Anticancer Res, 2017, 37(4): 1711-1722. DOI: 10.21873/anticanres.11503.
JACQUEMET G, PAATERO I, CARISEY A F, et al . FiloQuant reveals increased filopodia density during breast cancer progression[J ] . J Cell Biol, 2017, 216(10): 3387-3403. DOI: 10.1083/jcb.201704045.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621