Tumor Biology

, Volume 37, Issue 1, pp 1319–1325 | Cite as

Inhibition of human 67-kDa laminin receptor sensitizes multidrug resistance colon cancer cell line SW480 for apoptosis induction

  • Chun-Lei Lu
  • Jian Xu
  • Hao-Jie Yao
  • Kun-Lun Luo
  • Jie-Ming Li
  • Tao Wu
  • Guo-Zhong Wu
Original Article


The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.


Adhesion Apoptosis Colon cancer CMDR Laminin 


Conflicts of interest



  1. 1.
    Ota M, Takamura N, Irimura T. Involvement of cell surface glycans in adhesion of human colon carcinoma cells to liver tissue in a frozen section assay: role of endo-beta-galactosidase-sensitive structures. Cancer Res. 2000;60:5261–8.PubMedGoogle Scholar
  2. 2.
    Nelson J, McFerran NV, Pivato G, Chambers E, Doherty C, Steele D, et al. The 67 kDa laminin receptor: structure, function and role in disease. Biosci Rep. 2008;28:33–48.CrossRefPubMedGoogle Scholar
  3. 3.
    Timpl R, Rohde H, Robey PG, Rennard SI, Foidart JM, Martin GR. Laminin—a glycoprotein from basement membranes. J Biol Chem. 1979;254:9933–7.PubMedGoogle Scholar
  4. 4.
    Damiano JS. Integrins as novel drug targets for overcoming innate drug resistance. Curr Cancer Drug Targets. 2002;2:37–43.CrossRefPubMedGoogle Scholar
  5. 5.
    Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D, Choo C, et al. Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat Med. 1999;5:662–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Stupack DG, Cheresh DA. Get a ligand, get a life: integrins, signaling and cell survival. J Cell Sci. 2002;115:3729–38.CrossRefPubMedGoogle Scholar
  7. 7.
    Damiano JS, Hazlehurst LA, Dalton WS. Cell adhesion-mediated drug resistance (CAM-DR) protects the K562 chronic myelogenous leukemia cell line from apoptosis induced by BCR/ABL inhibition, cytotoxic drugs, and gamma-irradiation. Leukemia. 2001;15:1232–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Martin SS, Vuori K. Regulation of Bcl-2 proteins during anoikis and amorphosis. Biochim Biophys Acta. 2004;1692:145–57.CrossRefPubMedGoogle Scholar
  9. 9.
    Givant-Horwitz V, Davidson B, Reich R. Laminin-induced signaling in tumor cells. Cancer Lett. 2005;223:1–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Schmidmaier R, Baumann P. Anti-adhesion evolves to a promising therapeutic concept in oncology. Curr Med Chem. 2008;15:978–90.CrossRefPubMedGoogle Scholar
  11. 11.
    Ritthipichai K, Nan Y, Bossis I, Zhang Y. Viral FLICE inhibitory protein of rhesus monkey rhadinovirus inhibits apoptosis by enhancing autophagosome formation. PLoS ONE. 2012;7:e39438.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Patel D, Nan Y, Shen M, Ritthipichai K, Zhu X, Zhang YJ. Porcine reproductive and respiratory syndrome virus inhibits type I interferon signaling by blocking STAT1/STAT2 nuclear translocation. J Virol. 2010;84:11045–55.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Nan Y, Wang R, Shen M, Faaberg KS, Samal SK, Zhang YJ. Induction of type I interferons by a novel porcine reproductive and respiratory syndrome virus isolate. Virology. 2012;432:261–70.CrossRefPubMedGoogle Scholar
  14. 14.
    Humphries MJ. Cell adhesion assays. Methods Mol Biol. 2009;522:203–10.CrossRefPubMedGoogle Scholar
  15. 15.
    Moodley K, Weiss SF. Downregulation of the non-integrin laminin receptor reduces cellular viability by inducing apoptosis in lung and cervical cancer cells. PLoS ONE. 2013;8:e57409.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Guan JL, Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature. 1992;358:690–2.CrossRefPubMedGoogle Scholar
  17. 17.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993;74:609–19.CrossRefPubMedGoogle Scholar
  18. 18.
    Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226:1097–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986;47:19–28.CrossRefPubMedGoogle Scholar
  20. 20.
    Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988;335:440–2.CrossRefPubMedGoogle Scholar
  21. 21.
    Li A, Ojogho O, Escher A. Saving death: apoptosis for intervention in transplantation and autoimmunity. Clin Dev Immunol. 2006;13:273–82.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Fan D, Zhang X, Chen X, Mou Z, Hu J, Zhou S, et al. Bird’s-eye view on gastric cancer research of the past 25 years. J Gastroenterol Hepatol. 2005;20:360–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Hohenester E, Engel J. Domain structure and organisation in extracellular matrix proteins. Matrix Biol. 2002;21:115–28.CrossRefPubMedGoogle Scholar
  24. 24.
    Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93:1658–67.PubMedGoogle Scholar
  25. 25.
    Hazlehurst LA, Dalton WS. Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies. Cancer Metastasis Rev. 2001;20:43–50.CrossRefPubMedGoogle Scholar
  26. 26.
    Shain KH, Dalton WS. Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR. Mol Cancer Ther. 2001;1:69–78.PubMedGoogle Scholar
  27. 27.
    Hazlehurst LA, Argilagos RF, Emmons M, Boulware D, Beam CA, Sullivan DM, et al. Cell adhesion to fibronectin (CAM-DR) influences acquired mitoxantrone resistance in U937 cells. Cancer Res. 2006;66:2338–45.CrossRefPubMedGoogle Scholar
  28. 28.
    Timpl R. Macromolecular organization of basement membranes. Curr Opin Cell Biol. 1996;8:618–24.CrossRefPubMedGoogle Scholar
  29. 29.
    Kim WH, Lee BL, Jun SH, Song SY, Kleinman HK. Expression of 32/67-kDa laminin receptor in laminin adhesion-selected human colon cancer cell lines. Br J Cancer. 1998;77:15–20.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Giancotti FG, Ruoslahti E. Integrin signaling. Science. 1999;285:1028–32.CrossRefPubMedGoogle Scholar
  31. 31.
    Calderwood DA, Shattil SJ, Ginsberg MH. Integrins and actin filaments: reciprocal regulation of cell adhesion and signaling. J Biol Chem. 2000;275:22607–10.CrossRefPubMedGoogle Scholar
  32. 32.
    Plow EF, Haas TA, Zhang L, Loftus J, Smith JW. Ligand binding to integrins. J Biol Chem. 2000;275:21785–8.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Gastrointestinal SurgeryNo. 101 Hospital of PLAWuxiChina

Personalised recommendations