Invasive Cx43high sub-line of human prostate DU145 cells displays increased nanomechanical deformability

  • Katarzyna Piwowarczyk Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Michal Sarna Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland; Department of Medical Physics and Biophysics, Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Cracow, Poland
  • Damian Ryszawy Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
  • Jarosław Czyż Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University
Keywords: prostate cancer invasion, Cx43, cell elasticity, motility, AFM,

Abstract

Connexin(Cx)43high cells are preferentially recruited to the invasive front of prostate cancer in vitro and in vivo. To address the involvement of Cx43 in the regulation of human prostate cancer DU145 cell invasiveness, we analysed the nanoelasticity of invasive Cx43high sub-sets of DU145 cells by atomic force microscopy (AFM). Cx43high DU145 cells displayed considerably higher susceptibility to mechanical distortions than the wild type DU145 cells. Transient Cx43 silencing had no effect on their elastic properties. Our data confirm the relationship between invasive potential, Cx43 expression and nanomechanical elasticity of DU145 cells. However, they also show that Cx43 is not directly involved in the maintenance of DU145 invasive phenotype.

References

Baran B, Bechyne I, Siedlar M, Szpak K, Mytar B, Sroka J, Laczna E, Madeja Z, Zembala M, Czyz J (2009) Blood monocytes stimulate migration of human pancreatic carcinoma cells in vitro: the role of tumour necrosis factor - alpha. Eur J Cell Biol 88:743-752; doi: 10.1016/j.ejcb.2009.08.002.

Blick T, Widodo E, Hugo H, Waltham M, Lenburg ME, Neve RM, Thompson EW (2008) Epithelial mesenchymal transition traits in human breast cancer cell lines. Clin Exp Metastasis 25:629-642; doi: 10.1007/s10585-008-9170-6.

Cai X, Xing X, Cai J, Chen Q, Wu S, Huang F (2010) Connection between biomechanics and cytoskeleton structure of lymphocyte and Jurkat cells: An AFM study. Micron 41:257-262; doi: 10.1016/j.micron.2009.08.011.

Cronier L, Crespin S, Strale PO, Defamie N, Mesnil M (2009) Gap junctions and cancer: new functions for an old story. Antioxid Redox Signal 11:323-338; doi: 10.1089/ars.2008.2153.

Cross SE, Jin YS, Rao J, Gimzewski JK (2007) Nanomechanical analysis of cells from cancer patients. Nat Nanotechnol 2:780-783; doi: 10.1038/nnano.2007.388.

Czyz J (2008) The stage-specific function of gap junctions during tumourigenesis. Cell Mol Biol Lett 13:92-102; doi: 10.2478/s11658-007-0039-5.

Czyz J, Szpak K, Madeja Z (2012) The role of connexins in prostate cancer promotion and progression. Nat Rev Urol 9:274-282; doi: 10.1038/nrurol.2012.14.

Daniel-Wojcik A, Misztal K, Bechyne I, Sroka J, Miekus K, Madeja Z, Czyz J (2008) Cell motility affects the intensity of gap junctional coupling in prostate carcinoma and melanoma cell populations. Int J Oncol 33:309-315; doi: 10.3892/ijo_00000010.

Dufrene YF (2003) Recent progress in the application of atomic force microscopy imaging and force spectroscopy to microbiology. Curr Opin Microbiol 6:317-323; doi: 10.1016/S1369-5274(03)00058-4.

Friedl P and Wolf K (2010) Plasticity of cell migration: a multiscale tuning model. J Exp Med 207:11-19; doi: 10.1083/jcb.200909003.

Gupta GP and Massague J (2006) Cancer metastasis: building a framework. Cell 127:679-695; doi: 10.1016/j.cell.2006.11.001.

Ito A, Katoh F, Kataoka TR, Okada M, Tsubota N, Asada H, Yoshikawa K, Maeda S, Kitamura Y, Yamasaki H, Nojima H (2000) A role for heterologous gap junctions between melanoma and endothelial cells in metastasis. J Clin Invest 105:1189-1197; doi: 10.1172/JCI8257.

Kanczuga-Koda L, Sulkowski S, Lenczewski A, Koda M, Wincewicz A, Baltaziak M, Sulkowska M (2006) Increased expression of connexins 26 and 43 in lymph node metastases of breast cancer. J Clin Pathol 59:429-433; doi: 10.1136/jcp.2005.029272.

Kumar S and Weaver VM (2009) Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev 28:113-127; doi: 10.1007/s10555-008-9173-4.

Langley RR and Fidler IJ (2007) Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr Rev 28:297-321; doi: 10.1210/er.2006-0027.

Leithe E, Sirnes S, Omori Y, Rivedal E (2006) Downregulation of gap junctions in cancer cells. Crit Rev Oncog 12:225-256; doi: 10.1615/CritRevOncog.v12.i3-4.30.

Li QS, Lee GY, Ong CN, Lim CT (2008) AFM indentation study of breast cancer cells. Biochem Biophys Res Commun 374:609-613; doi: 10.1016/j.bbrc.2008.07.078.

Maeda S and Tsukihara T (2011) Structure of the gap junction channel and its implications for its biological functions. Cell Mol Life Sci 68:1115-1129; doi: 10.1007/s00018-010-0551-z.

Miekus K, Czernik M, Sroka J, Czyz J, Madeja Z (2005) Contact stimulation of prostate cancer cell migration: the role of gap junctional coupling and migration stimulated by heterotypic cell-to-cell contacts in determination of the metastatic phenotype of Dunning rat prostate cancer cells. Biol Cell 97:893-903; doi: 10.1042/BC20040129.

Mol AJ, Geldof AA, Meijer GA, van der Poel HG, van Moorselaar RJ (2007) New experimental markers for early detection of high-risk prostate cancer: role of cell-cell adhesion and cell migration. J Cancer Res Clin Oncol 133:687-695; doi: 10.1007/s00432-007-0235-8.

Naus CC and Laird DW (2010) Implications and challenges of connexin connections to cancer. Nat Rev Cancer 10:435-441; doi: 10.1038/nrc2841.

Olk S, Zoidl G, Dermietzel R (2009) Connexins, cell motility, and the cytoskeleton. Cell Motil Cytoskeleton 66:1000-1016; doi: 10.1002/cm.20404.

Piwowarczyk K, Wybieralska E, Baran J, Borowczyk J, Rybak P, Kosinska M, Wlodarczyk AJ, Michalik M, Siedlar M, Madeja Z, Dobrucki J, Reiss K, Czyz J (2015) Fenofibrate enhances barrier function of endothelial continuum within the metastatic niche of prostate cancer cells. Expert Opin Ther Targets Expert. Opin. Ther. Targets. 19:163-76; doi: 10.1517/14728222.2014.981153.

Pollmann MA, Shao Q, Laird DW, Sandig M (2005) Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture. Breast Cancer Res 7:R522-R534; doi: 10.1186/bcr1042.

Prochnow N and Dermietzel R (2008) Connexons and cell adhesion: a romantic phase. Histochem Cell Biol 130:71-77; doi: 10.1007/s00418-008-0434-7.

Radmacher M, Fritz M, Kacher CM, Cleveland JP, Hansma PK (1996) Measuring the viscoelastic properties of human platelets with the atomic force microscope. Biophysical Journal 70:556-567; doi: 10.1016/S0006-3495(96)79602-9.

Ryszawy D, Sarna M, Rak M, Szpak K, Kedracka-Krok S, Michalik M, Siedlar M, Zuba-Surma E, Burda K, Korohoda W, Madeja Z, Czyz J (2014) Functional links between Snail-1 and Cx43 account for the recruitment of Cx43-positive cells into the invasive front of prostate cancer. Carcinogenesis. 35:1920-30; doi: 10.1093/carcin/bgu033.

Shibata M and Shen MM (2013) The roots of cancer: Stem cells and the basis for tumor heterogeneity. Bioessays 35:253-260; doi: 10.1002/bies.201200101.

Sottoriva A, Verhoeff JJ, Borovski T, McWeeney SK, Naumov L, Medema JP, Sloot PM, Vermeulen L (2010) Cancer stem cell tumor model reveals invasive morphology and increased phenotypical heterogeneity. Cancer Res 70:46-56; doi: 10.1158/0008-5472.CAN-09-3663.

Suresh S (2007) Biomechanics and biophysics of cancer cells. Acta Biomater 3:413-438; doi: 10.1016/j.actbio.2007.04.002.

Szpak K, Wybieralska E, Niedzialkowska E, Rak M, Bechyne I, Michalik M, Madeja Z, Czyz J (2011) DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express elevated levels of CX43. Cell Mol Biol Lett 16:625-37; doi: 10.2478/s11658-011-0027-7.

Touhami A, Nysten B, Dufrene YF (2003) Nanoscale mapping of the elasticity of microbial cells by atomic force microscopy. Langmuir 19:4539-4543; doi: 10.1021/la034136x.

Watanabe N, Dickinson DA, Krzywanski DM, Iles KE, Zhang H, Venglarik CJ, Forman HJ (2002) A549 subclones demonstrate heterogeneity in toxicological sensitivity and antioxidant profile. Am J Physiol Lung Cell Mol Physiol 283:L726-L736; doi: 10.1152/ajplung.00025.2002.

Zhang W, DeMattia JA, Song H, Couldwell WT (2003) Communication between malignant glioma cells and vascular endothelial cells through gap junctions. J Neurosurg 98:846-853; doi: 10.3171/jns.2003.98.4.0846.

Published
2017-06-24
Section
Articles