Gastric cancer cell adhesion to laminin enhances acquired chemotherapeutic drug resistance mediated by MGr1-Ag/37LRP

被引：15

作者：

Sun, Li ^{[1
]}

Liu, Lili ^{[2
]}

Liu, Xiangqiang ^{[1
]}

Wang, Yafang ^{[2
]}

Li, Mengbin ^{[1
]}

Yao, Liping ^{[1
]}

Yang, Jianjun ^{[1
]}

Ji, Genlin ^{[3
]}

Guo, Changcun ^{[1
]}

Pan, Yanglin ^{[1
]}

Liang, Shuhui ^{[1
]}

Wang, Biaoluo ^{[1
]}

Ding, Jie ^{[1
]}

Zhang, Hongwei ^{[1
]}

Shi, Yongquan ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp Digest Dis, State Key Lab Canc Biol, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Tangdu Hosp, Dept Oncol, Xian 710038, Peoples R China

[3] Fourth Mil Med Univ, Xijing Hosp, Dept Anesthesiol, Xian 710032, Peoples R China

来源：

ONCOLOGY REPORTS | 2014年 / 32卷 / 01期

关键词：

MGr1-Ag/37LRP; CAM-DR; gastric cancer; laminin; cell adhesion; MULTIDRUG-RESISTANCE; RECEPTOR PRECURSOR; MULTIPLE-MYELOMA; EXPRESSION; PROTEIN; ORGANIZATION; CONTRIBUTES; MECHANISM; APOPTOSIS; GROWTH;

D O I：

10.3892/or.2014.3184

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Adhesion of cancer cells to the extracellular matrix (ECM) causes a novel acquired chemotherapeutic drug-resistant phenotype, referred to as cell adhesion-mediated drug resistance (CAM-DR). Our previous studies suggested that the adhesion molecule MGr1-Ag/37LRP may promote multidrug resistance in gastric cancer cells. Therefore, we investigated MGr1-Ag/37LRP binding-induced adhesion, and its role in CAM-DR. Initial studies revealed that, after adhesion to the ECM, the multidrug-resistant gastric cancer cell lines SGC7901/VCR and SGC7901/ADR showed significantly higher mean adhesive cell numbers than non-resistant SGC7901 cells. We then investigated expression of MGr1-Ag/37LRP in gastric cancer cells adhering to laminin. Western blotting, RT-PCR and dual-luciferase reporter assays showed that laminin induced MGr1-Ag/37LRP expression and activity. In vitro and in vivo assays revealed that small interfering RNA against MGr1-Ag/37LRP significantly reduced CAM-DR in SGC7901/VCR cells. In vivo and in vitro analyses revealed that binding of MGr1-Ag/37LRP decreased intracellular drug accumulation by increasing P-glycoprotein and multidrug-associated protein expression, and inhibited drug-induced apoptosis by regulating Bcl-2 and Bax expression. These results indicate that MGr1-Ag/37LRP contributes to laminin-mediated CAM-DR in gastric cancer cells, and is a potentially effective target for reversing this phenomenon in gastric cancer.

引用

页码：105 / 114

页数：10

共 25 条

[1] Extracellular matrix and integrin signalling: the shape of things to come [J].

Boudreau, J ;

Jones, PL .

BIOCHEMICAL JOURNAL, 1999, 339 :481-488

[2]

Cai XJZX., 1994, CHIN J CLIN ONCOL S, P67

[3] Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines [J].

Damiano, JS ;

Cress, AE ;

Hazlehurst, LA ;

Shtil, AA ;

Dalton, WS .

BLOOD, 1999, 93 (05) :1658-1667

[4]

DAVID L, 1994, CANCER, V73, P518, DOI 10.1002/1097-0142(19940201)73:3<518::AID-CNCR2820730305>3.0.CO

[5]

2-T

[6]

FAN DM, 1998, WORLD J GASTROENT S2, V4, P110

[7]

Fan KC, 2000, ANTICANCER RES, V20, P4809

[8]

Filleur S, 2003, CANCER RES, V63, P3919

[9]

Gleave M, 1999, CLIN CANCER RES, V5, P2891

[10] Domain structure and organisation in extracellular matrix proteins [J].

Hohenester, E ;

Engel, J .

MATRIX BIOLOGY, 2002, 21 (02) :115-128

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