Preferences help
enabled [disable] Abstract
Number of results
2010 | 57 | 3 | 269-275
Article title

DNAzyme as an efficient tool to modulate invasiveness of human carcinoma cells

Title variants
Languages of publication
In this study we evaluated efficiency of DNAzymes to modulate motility of cancer cells, an important factor in the progression and metastasis of cancers. For this purpose we targeted β1 integrins that are predominant adhesive receptors in various carcinoma cell lines (CX1.1, HT29, LOVO, LS180, PC-3). To evaluate invasiveness of cancer cells, we used a transwell migration assay that allowed analyzing chemotactic migration of colon carcinoma cell lines across an ECM-coated membrane. Their adhesive properties were also characterized by the analysis of adhesion to fibronectin, laminin and collagen. In addition, the expression of major integrin subunits, selected intact β1 integrins, and other adhesive receptors (ICAM, E-selectin, uPAR) was analyzed by flow cytometry. Inhibition of β1 integrin expression by DNAzyme to β1 mRNA almost abolished the invasiveness of the CX1.1, HT29, LS180, LOVO and PC-3 cells in vitro. These data show that DNAzymes to β1 integrin subunit can be used to inhibit invasiveness of carcinoma cells.
Physical description
  • Department of Molecular and Medical Biophysics, Medical University of Łódź, Łódź, Poland
  • Department of Molecular and Medical Biophysics, Medical University of Łódź, Łódź, Poland
  • Department of Bioorganic Chemistry, Centre for Molecular and Macromolecular Studies, Polish Academy of Sciences, Łódź, Poland
  • Department of Molecular and Medical Biophysics, Medical University of Łódź, Łódź, Poland
  • Department of Molecular and Medical Biophysics, Medical University of Łódź, Łódź, Poland
  • Borradori L, Sonnenberg AJ (1999) Structure and function of hemidesmosomes: more than simple adhesion complexes. J Invest Dermatol 112: 411-418.
  • Chan CW, Khachigian LM (2009) DNAzymes and their therapeutic possibilities. Intern Med J 39: 249-251.
  • Chen Q, Manning CD, Millar H, McCabe FL, Ferrante C, Sharp C, Shahied-Arruda L, Doshi P, Nakada MT, Anderson GM (2008) CNTO 95, a fully human anti alphav integrin antibody, inhibits cell signaling, migration, invasion, and spontaneous metastasis of human breast cancer cells. Clin Exp Metastasis 25: 139-148.
  • Cierniewski CS, Babinska A, Swiatkowska M, Wilczynska M, Okruszek A, Stec W (1995) Inhibition by modified oligodeoxynucleotides of the expression of type-1 plasminogen activator inhibitor in human endothelial cells. Eur J Biochem 227: 494-499.
  • Cieslak M, Niewiarowska J, Nawrot M, Koziolkiewicz M, Stec WJ, Cierniewski CS (2002) DNAzymes to beta 1 and beta 3 mRNA down-regulate expression of the targeted integrins and inhibit endothelial cell capillary tube formation in fibrin and matrigel. J Biol Chem 277: 6779-6787.
  • Cieslak M, Szymanski J, Adamiak RW, Cierniewski CS (2003) Structural rearrangements of the '10-23'DNAzyme to β3 integrin subunit mRNA induced by cations and their relations to the catalytic activity. J Biol Chem 278: 47987-47996.
  • Dass CR, Choong PF, Khachigian LM (2008a) DNAzyme technology and cancer therapy: cleave and let die. Mol Cancer Ther 7: 243-251.
  • Dass K, Ahmad A, Azmi AS, Sarkar SH, Sarkar FH (2008b) Evolving role of uPA/uPAR system in human cancers. Cancer Treat Rev 34: 122-136.
  • Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2: 161-174.
  • Felding-Habermann B, Mueller BM, Romerdahl CA, Cheresh DA (1992) Involvement of integrin alpha V gene expression in human melanoma tumorigenicity. J Clin Invest 89: 2018-2022.
  • Fidler IJ, Kumar R, Bielenberg DR, Ellis LM (1998) Molecular determinants of angiogenesis in cancer metastasis. Cancer J Sci Am 4: S58-S66.
  • Giannelli G, Bergamini C, Fransvea E, Marinosci F, Quaranta V, Antonaci S (2001) Human hepatocellular carcinoma (HCC) cells require both α3β1 integrin and matrix metalloproteinases activity for migration and invasion. Lab Invest 81: 613-627.
  • Giannelli G, Astigiano S, Antonaci S, Morini M, Barbieri O, Noonan DM, Albini A (2002) Role of the alpha3beta1 and alpha6beta4 integrins in tumor invasion. Clin Exp Metastasis 19: 217-223.
  • Goel HL, Li J, Kogan S, Languino LR (2008) Integrins in prostate cancer progression. Endocr Relat Cancer 15: 657-664.
  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57-70.
  • Haier J, Nasralla M, Buhr HJ, Nicolson GL (1998) Different integrin-induced adhesion of highly liver metastatic and little metastatic colon carcinoma cells in an extracellular matrix. Langenbecks Arch Chir Suppl Kongressbd 115: 307-313.
  • Hodgkinson CP, Wright MC, Paine AJ (2000) Fibronectin-mediated hepatocyte shape change reprograms cytochrome P450 2C11 gene expression via an integrin-signaled induction of ribonuclease activity. Mol Pharmacol 58: 976-981.
  • Ise H, Sugihara N, Negishi N, Nikaido T, Akaike T (2001) Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes. Biochem Biophys Res Commun 285: 172-182.
  • Jones JC, Hopkinson SB, Goldfinger LE (1998) Hemidesmosomes: extracellular matrix/intermediate filament connectors. BioEssays 20: 488-494.
  • Kagami S, Kuhara T, Yasutomo K, Okada K, Loster K, Reutter W, Kuroda Y (1996) Transforming growth factor-β (TGF-β) stimulates the expression of β1 integrins and adhesion by rat mesangial cells. Exp Cell Res 229: 1-6.
  • Kassis J, Lauffenburger DA, Turner T, Wells A (2001) Tumor invasion as dysregulated cell motility. Semin Cancer Biol 11: 105-117.
  • Kawakami-Kimura N, Narita T, Ohmori K, Yoneda T, Matsumoto K, Nakamura T, Kannagi R (1997) Involvement of hepatocyte growth factor in increased integrin expression on HepG2 cells triggered by adhesion to endothelial cells. Br J Cancer 75: 47-53.
  • Kielosto M, Nummela P, Järvinen K, Yin M, Hölttä E (2009) Identification of integrins alpha6 and beta7 as c-Jun- and transformation-relevant genes in highly invasive fibrosarcoma cells. Int J Cancer 125: 1065-1073.
  • Kruskal JB, Azouz A, Korideck H, El-Hallak M, Robson SC, Thomas P, Goldberg SN (2007) Hepatic colorectal cancer metastases: imaging initial steps of formation in mice. Radiology 243: 703-711.
  • Liotta LA, Kohn EC (2001) The microenvironment of the tumour-host interface. Nature (Lond.) 411: 375-379.
  • Lohi J (2001) Laminin-5 in the progression of carcinomas. Int J Cancer 94: 763-767.
  • Maglott AP, Bartik S, Cosgun P, Klotz P, Ronde G, Fuhrmann K, Takeda SM, Dontenwill M (2006) The small alpha5beta1 integrin antagonist, SJ749, reduces proliferation and clonogenicity of human astrocytoma cells. Cancer Res 66: 6002-6007.
  • Mercurio AM, Bachelder RE, Chung J, O'Connor KL, Rabinovitz I, Shaw LM, Tani T (2001) Integrin laminin receptors and breast carcinoma progression. J Mammary Gland Biol Neoplasia 6: 299-309.
  • Oliva IB, Coelho RM, Barcellos GG, Saldanha-Gama R, Wermelinger LS, Marcinkiewicz C, Zingali B, Barja-Fidalgo C (2007) Effect of RGD-disintegrins on melanoma cell growth and metastasis: involvement of the actin cytoskeleton, FAK and c-Fos. Toxicon 50: 1053-1063.
  • Papiewska-Pajak I, Antoszczyk S (2006) Regulation of beta1 integrin expression in endothelial cells by chimeric tRNA(Val) ribozyme. Acta Biochim Pol 53: 311-316.
  • Park CC, Zhang H, Pallavicini M, Gray JW, Baehner F, Park CJ, Bissell MJ (2006) Beta1 integrin inhibitory antibody induces apoptosis of breast cancer cells, inhibits growth, and distinguishes malignant from normal phenotype in three dimensional cultures and in vivo. Cancer Res 66: 1526-1535.
  • Qian F, Zhang ZC, Wu XF, Li YP, Xu Q (2005) Interaction between integrin alpha(5) and fibronectin is required for metastasis of B16F10 melanoma cells. Biochem Biophys Res Commun 333: 1269-1275.
  • Quaranta V (2002) Motility cues in the tumor microenvironment. Differentiation 70: 590-598.
  • Radisky D, Hagios C, Bissell MJ (2001) Tumors are unique organs defined by abnormal signaling and context. Semin Cancer Biol 11: 87-95.
  • Sabherwal Y, Rothman VL, Dimitrov S, L'Heureux DZ, Marcinkiewicz C, Sharma M, Tuszynski GP (2006) Integrin alpha2beta1 mediates the anti-angiogenic and anti-tumor activities of angiocidin, a novel tumor-associated protein. Exp Cell Res 312: 2443-2453.
  • Sawhney RS, Zhou G-HK, Humphrey LE, Ghosh P, Kreisberg JI, Brattain MG. J (2002) Differences in sensitivity of biological functions mediated by epidermal growth factor receptor activation with respect to endogenous and exogenous ligands. J Biol Chem 277: 75-86.
  • Schaffert CS, Sorrell MF, Tuma DJ (2001) Expression and cytoskeletal association of integrin subunits is selectively increased in rat perivenous hepatocytes after chronic ethanol administration. Alcohol Clin Exp Res 25: 1749-1757.
  • Simon-Assmann P, Leberquier C, Molto N, Uezato T, Bouziges F, Kedinger M (1994) Adhesive properties and integrin expression profiles of two colonic cancer populations differing by their spreading on laminin. J Cell Sci 107: 577-587.
  • Smida Rezgui S, Honore S, Rognoni JB, Martin PM, Penel C (2000) Up-regulation of α2β1 integrin cell-surface expression protects A431 cells from epidermal growth factor-induced apoptosis. Int J Cancer 87: 360-367.
  • Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9: 541-573.
  • Torimura T, Ueno T, Kin M, Harad R, Nakamura T, Sakamoto M, Kumashiro R, Yano H, Kojiro M, Sata M (2001) Laminin deposition to type IV collagen enhances haptotaxis, chemokinesis, and adhesion of hepatoma cells through β1-integrins. J Hepatol 35: 245-253.
  • Yao ES, Zhang H, Chen YY, Lee B, Chew K, Moore D, Park C (2007) Increased B1 integrin is associated with decreased survival in invasive breast cancer. Cancer Res 67: 659-664.
  • Yuan ST, Hu XQ, Lu JP, KeiKi H, Zhai WR, Zhang YE (2000) Changes of integrin expression in rat hepatocarcinogenesis induced by 3'-Me-DAB. World J Gastroenterol 6: 231-233.
  • Zeng ZZ, Jia Y, Hahn NJ, Markwart SM, Rockwood KF, Livant DL (2006) Role of focal adhesion kinase and phosphatidylinositol 3'-kinase in integrin fibronectin receptor-mediated, matrix metalloproteinase-1-dependent invasion by metastatic prostate cancer cells. Cancer Res 66: 8091-8099.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.