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

Sun,Li; Liu,Lili; Liu,Xiangqiang; Wang,Yafang; Li,Mengbin; Yao,Liping; Yang,Jianjun; Ji,Genlin; Guo,Changcun; Pan,Yanglin; Liang,Shuhui; Wang,Biaoluo; Ding,Jie; Zhang,Hongwei; Shi,Yongquan

doi:10.3892/or.2014.3184

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

Authors:
- Li Sun
- Lili Liu
- Xiangqiang Liu
- Yafang Wang
- Mengbin Li
- Liping Yao
- Jianjun Yang
- Genlin Ji
- Changcun Guo
- Yanglin Pan
- Shuhui Liang
- Biaoluo Wang
- Jie Ding
- Hongwei Zhang
- Yongquan Shi
View Affiliations

Affiliations: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, P.R. China, Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China, Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, P.R. China
Published online on: May 15, 2014 https://doi.org/10.3892/or.2014.3184
Pages: 105-114

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Fan DM, Xiao B, Shi YQ, Ming-Feng, Qiao TD, Chen BJ and Chen Z: A novel cDNA fragment associated with gastric cancer drug resistance was screened out from a library by monoclonal antibody MGr1. World J Gastroenterol. 4:110–111. 1998.
2	Shi Y, Zhai H, Wang X, et al: Multidrug-resistance-associated protein MGr1-Ag is identical to the human 37-kDa laminin receptor precursor. Cell Mol Life Sci. 59:1577–1583. 2002. View Article : Google Scholar : PubMed/NCBI
3	Sun L, Shi Y, Guo C, et al: Regulation of multidrug resistance by MGr1-antigen in gastric cancer cells. Tumour Biol. 27:27–35. 2006. View Article : Google Scholar : PubMed/NCBI
4	Boudreau NJ and Jones PL: Extracellular matrix and integrin signalling: the shape of things to come. Biochem J. 339:481–488. 1999. View Article : Google Scholar : PubMed/NCBI
5	Damiano JS, Cress AE, Hazlehurst LA, Shtil AA and Dalton WS: Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 93:1658–1667. 1999.PubMed/NCBI
6	Nakamura K, Mori M and Enjoji M: Distribution of basement membrane antigens in clinical gastric adenocarcinomas: an immunohistochemical study. J Clin Pathol. 40:1418–1423. 1987. View Article : Google Scholar : PubMed/NCBI
7	Kawaguchi M, Akagi M, Gray MJ, Liu W, Fan F and Ellis LM: Regulation of vascular endothelial growth factor expression in human gastric cancer cells by interleukin-1β. Surgery. 136:686–692. 2004.
8	Jaseja M, Mergen L, Gillette K, Forbes K, Sehgal I and Copié V: Structure-function studies of the functional and binding epitope of the human 37 kDa laminin receptor precursor protein. J Pept Res. 66:9–18. 2005. View Article : Google Scholar : PubMed/NCBI
9	Cai X, Zhang X and Fan D: Establishment of multidrug resistant gastric cancer cell line and its biological characteristics. Chin J Clin Oncol. 2S:67–71. 1994.(in Chinese with English abstract).
10	Liu L, Zhang H, Sun L, et al: ERK/MAPK activation involves hypoxia-induced MGr1-Ag/37LRP expression and contributes to apoptosis resistance in gastric cancer. Int J Cancer. 127:820–829. 2010.PubMed/NCBI
11	Liu L, Sun L, Zhang H, et al: Hypoxia-mediated up-regulation of MGr1-Ag/37LRP in gastric cancers occurs via hypoxia-inducible-factor 1-dependent mechanism and contributes to drug resistance. Int J Cancer. 124:1707–1715. 2009. View Article : Google Scholar : PubMed/NCBI
12	Fan K, Fan D, Cheng LF and Li C: Expression of multidrug resistance-related markers in gastric cancer. Anticancer Res. 20:4809–4814. 2000.PubMed/NCBI
13	Thamilselvan V and Basson MD: Pressure activates colon cancer cell adhesion by inside-out focal adhesion complex and actin cytoskeletal signaling. Gastroenterology. 126:8–18. 2004. View Article : Google Scholar : PubMed/NCBI
14	Li J, Xu LZ, He KL, et al: Reversal effects of nomegestrol acetate on multidrug resistance in adriamycin-resistant MCF7 breast cancer cell line. Breast Cancer Res. 3:253–263. 2001. View Article : Google Scholar : PubMed/NCBI
15	Filleur S, Courtin A, Ait-Si-Ali S, et al: SiRNA-mediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogenic thrombospondin-1 and slows tumor vascularization and growth. Cancer Res. 63:3919–3922. 2003.
16	Kuo CC, Hsieh HP, Pan WY, et al: BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 64:4621–4628. 2004. View Article : Google Scholar
17	Gleave M, Tolcher A, Miyake H, et al: Progression to androgen independence is delayed by adjuvant treatment with antisense Bcl-2 oligodeoxynucleotides after castration in the LNCaP prostate tumor model. Clin Cancer Res. 5:2891–2898. 1999.
18	Romanov VI, Wrathall LS, Simmons TD, Pinto da Silva P and Sobel ME: Protein synthesis is required for laminin-induced expression of the 67-kDa laminin receptor and its 37-kDa precursor. Biochem Biophys Res Commun. 208:637–643. 1995. View Article : Google Scholar : PubMed/NCBI
19	Noborio-Hatano K, Kikuchi J, Takatoku M, et al: Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene. 28:231–242. 2009. View Article : Google Scholar : PubMed/NCBI
20	Kobune M, Chiba H, Kato J, et al: Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism. Mol Cancer Ther. 6:1774–1784. 2007. View Article : Google Scholar : PubMed/NCBI
21	Hohenester E and Engel J: Domain structure and organisation in extracellular matrix proteins. Matrix Biol. 21:115–128. 2002. View Article : Google Scholar : PubMed/NCBI
22	Timpl R: Macromolecular organization of basement membranes. Curr Opin Cell Biol. 8:618–624. 1996. View Article : Google Scholar : PubMed/NCBI
23	David L, Nesland JM, Holm R and Sobrinho-Simões M: Expression of laminin, collagen IV, fibronectin, and type IV collagenase in gastric carcinoma. An immunohistochemical study of 87 patients. Cancer. 73:518–527. 1994. View Article : Google Scholar : PubMed/NCBI
24	Westhoff MA and Fulda S: Adhesion-mediated apoptosis resistance in cancer. Drug Resist Updat. 12:127–136. 2009. View Article : Google Scholar : PubMed/NCBI