Skip to main content
SpringerLink
Log in

Glioma Cells Promote the Expression of Vascular Cell Adhesion Molecule-1 on Bone Marrow-Derived Mesenchymal Stem Cells: a Possible Mechanism for Their Tropism Toward Gliomas

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The tropism of bone marrow-derived mesenchymal stem cells (BMSCs) toward gliomas has been shown by in vitro and in vivo assays. This study was carried out to evaluate the role of vascular cell adhesion molecule-1 (VCAM-1) in the migration of BMSCs towards glioma and the effect of glioma cells on the VCAM-1 expression of BMSCs. BMSCs were isolated according to their adherence to plastic. The tropism of BMSCs toward C6 and U87 glioma and the role of VCAM-1 in this migration were analyzed by in vitro migration assay, separately. Reverse transcription-polymerase chain reaction, immunofluorescence, and Western blot were employed to assess VCAM-1 expression of BMSCs when they were incubated by the conditioned mediums (CM) of C6 or U87 glioma cells. Data revealed that C6 and U87 glioma cells promote the migration of BMSCs, which could be blocked by a VCAM-1-neutralizing antibody. Moreover, VCAM-1 expression of BMSCs was elevated by the incubation of their CM. The results also demonstrated that LY294002, an inhibitor of phosphoinositide-3-kinase (PI3K), significantly inhibited the glioma-induced upregulation of VCAM-1 on BMSCs. These findings suggested that glioma-induced change in VCAM-1 expression of BMSCs may play an important role in their tropism towards glioma, and PI3K is associated with the signal transduction of this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aboody K, Brown A, Rainov N (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97:12846–12851

    Article  PubMed  CAS  Google Scholar 

  • Birnbaum T, Roider J, Schankin CJ, Padovan CS, Schichor C, Goldbrunner R, Straube A (2007) Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J Neurooncol 83:241–247

    Article  PubMed  CAS  Google Scholar 

  • Cheng P, Gao ZQ, Liu YH, Xue YX (2009) Platelet-derived growth factor BB promotes the migration of bone marrow-derived mesenchymal stem cells towards C6 glioma and up-regulates the expression of intracellular adhesion molecule-1. Neurosci Lett 451:52–56

    Article  PubMed  CAS  Google Scholar 

  • Ding W, Knox TR, Tschumper RC, Wu W, Schwager SM, Boysen JC, Jelinek DF, Kay NE (2010) Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia: implications for an angiogenic switch. Blood 116:2984–2993

    Article  PubMed  CAS  Google Scholar 

  • Ehtesham M, Kabos P, Gutierrez MA, Chung NH, Griffith TS, Black KL, Yu JS (2002) Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 62:7170–7174

    PubMed  CAS  Google Scholar 

  • Fischer-Valuck BW, Barrilleaux BL, Phinney DG, Russell KC, Prockop DJ, O’Conno KC (2010) Migratory response of mesenchymal stem cells to macrophage migration inhibitory factor and its antagonist as a function of colony-forming efficiency. Biotechnol Lett 32:19–27

    Article  PubMed  CAS  Google Scholar 

  • Forte G, Minieri M, Cossa P, Antenucci D, Sala M, Gnocchi V, Fiaccavento R, Carotenuto F, De Vito P, Baldini PM, Prat M, Di Nardo P (2006) Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells 24:23–33

    Article  PubMed  CAS  Google Scholar 

  • Ho IAW, Chan KYW, Ng W-H, Guo CM, Hui KM, Cheang P, Lam PYP (2009) Matrix metalloproteinase 1 is necessary for the migration of human bone marrow-derived mesenchymal stem cells toward human glioma. Stem Cells 27:1366–1375

    Article  PubMed  CAS  Google Scholar 

  • Hyun Y-M, Chung H-L, McGrath JL, Waugh RE, Kim M (2009) Activated integrin VLA-4 localizes to the lamellipodia and mediates T cell migration on VCAM-1. J Immunol 183:359–369

    Article  PubMed  CAS  Google Scholar 

  • Jiang B, Xu S, Hou X, Pimentel DR, Cohen RA (2004) Angiotensin II differentially regulates interleukin-1-beta-inducible NO synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) expression: role of p38 MAPK. J Biol Chem 279:20363–20368

    Article  PubMed  CAS  Google Scholar 

  • Klemke M, Weschenfelder T, Konstandin MH, Samstag Y (2007) High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers. J Cell Physiol 212:368–374

    Article  PubMed  CAS  Google Scholar 

  • Lau CJ, Koty Z, Nalbantoglu J (2009) Differential response of glioma cells to FOXO1-directed therapy. Cancer Res 69:5433–5440

    Article  PubMed  CAS  Google Scholar 

  • Mäenpää A, Kovanen PE, Paetau A, Jäáskeläinen J, Timonen T (1997) Lymphocyte adhesion molecule ligands and extracellular matrix proteins in gliomas and normal brain: expression of VCAM-1 in gliomas. Acta Neuropathol 94:216–225

    Article  PubMed  Google Scholar 

  • Menon LG, Picinich S, Koneru R, Ggo H, Lin SY, Koneru M, Mayer-Kuchku P, Glod J (2007) Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells 25:520–528

    Article  PubMed  CAS  Google Scholar 

  • Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65:3307–3318

    PubMed  CAS  Google Scholar 

  • Okkenhaug K, Vanhaesebroeck B (2003) PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 3:317–330

    Article  PubMed  CAS  Google Scholar 

  • Ponte ALL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, Charbord P, Domenech J, Langonné A, Hérault O (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25:1737–1745

    Article  PubMed  CAS  Google Scholar 

  • Redaelli M, Franceschi V, Capocefalo A, D’Avella D, Denaro L, Cavirani S, Mucignat-Caretta C, Donofrio G (2012) Herpes simplex virus type 1 thymidine kinase–armed bovine herpesvirus type 4–based vector displays enhanced oncolytic properties in immunocompetent orthotopic syngenic mouse and rat glioma models. Neuro Oncol 14:288–301

    Article  PubMed  Google Scholar 

  • Rosenman SJ, Shrikant P, Dubb L, Benveniste EN, Ransohoff RM (1995) Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. J Immunol 154:1888–1889

    PubMed  CAS  Google Scholar 

  • Rüster B, Göttig S, Ludwig RJ, Bistrian R, Müller S, Seifried E, Gille J, Henschler R (2006) Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells. Blood 108:3938–3944

    Article  PubMed  Google Scholar 

  • Ryu CH, Park S-H, Park SA, Kim SM, Lim JY, Jeong CH, Yoon W-S, W-il Oh, Sung YC, Jeun S-S (2011) Gene therapy of intracranial glioma using interleukin 12-secreting human umbilical cord blood-derived mesenchymal stem cells. Hum Gene Ther 22:733–743

    Article  PubMed  CAS  Google Scholar 

  • Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–766

    Article  PubMed  Google Scholar 

  • Sasportas LS, Kasmieh R, Wakimoto H, Hingtgen S, van de Water JA, Mohapatra G, Figueiredo JL, Martuza RL, Weissleder R, Shah K (2009) Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA 106:4822–4827

    Article  PubMed  CAS  Google Scholar 

  • Schichor C, Birnbaum T, Etminan N, Schnell O, Grau S, Miebach S, Aboody K, Padovan C, Straube A, Tonn JC, Goldbrunner R (2006) Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC). Exp Neurol 199:301–310

    Article  PubMed  CAS  Google Scholar 

  • Scrima M, Marco CD, Fabiani F, Franco R (2012) Signaling networks associated with AKT activation in non-small cell lung cancer (NSCLC): new insights on the role of phosphatydil-inositol-3 kinase. PLoS One 7:e30427

    Article  PubMed  CAS  Google Scholar 

  • Segers VFM, Van Riet I, Andries LJ, Lemmens K, Demolder MJ, De Becker AJML, Kockx MM, De Keulenaer GW (2006) Mesenchymal stem cell adhesion to cardiac microvascular endothelium: activators and mechanisms. Am J Physiol Heart Circ Physiol 290:H1370–H1377

    Article  PubMed  CAS  Google Scholar 

  • Snykers S, Vanhaecke T, Rogiers V (2006) Isolation of rat bone marrow stem cells. Methods Mol Biol 320:265–272

    PubMed  Google Scholar 

  • Steingen C, Brenig F, Baumgartner L, Schmidt J, Schmidt A, Bloch W (2008) Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells. J Mol Cell Cardiol 44:1072–1084

    Article  PubMed  CAS  Google Scholar 

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  • Tohill M, Mantovani C, Wiberg M, Terenghi G (2004) Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett 362:200–203

    Article  PubMed  CAS  Google Scholar 

  • Tsoyi K, Jang HJ, Nizamutdinova IT, Park K, Kim YM, Kim HJ, Seo HG, Lee JH, Chang KC (2010) PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3beta/GATA-6 signaling pathways in TNF-alpha-activated human endothelial cells. Atherosclerosis 213:115–121

    Article  PubMed  CAS  Google Scholar 

  • Uchibori R, Okada T, Ito T, Urabe M, Mizukami H, Kume A, Ozawa K (2009) Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy. J Gene Med 11:373–381

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Feuerstein GZ, Gu J-L, Lysko PG, Yue T-L (1995) Interleukin-1β induces expression of adhesion molecules in human vascular smooth muscle cells and enhances adhesion of leukocytes to smooth muscle cells. Atherosclerosis 115:89–98

    Article  PubMed  CAS  Google Scholar 

  • Ward SG, Westwick J, Harris S (2011) Sat-Nav for T cells: role of PI3K isoforms and lipid phosphatases in migration of T lymphocytes. Immunol Lett 138:15–18

    Article  PubMed  CAS  Google Scholar 

  • Wewer C, Seibt A, Wolburg H, Greune L, Schmidt MA, Berger J, Galla H-J, Quitsch U, Schwerk C, Schroten H, Tenenbaum T (2011) Transcellular migration of neutrophil granulocytes through the blood-cerebrospinal fluid barrier after infection with Streptococcus suis. J Neuroinflammation 8:51

    Article  PubMed  CAS  Google Scholar 

  • Xu F, Shi J, Yu B, Ni W, Wu X, Gu Z (2010) Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro. Oncol Rep 23:1561–1567

    PubMed  CAS  Google Scholar 

  • Yang B, Wu X, Mao Y, Bao W, Gao L, Zhou P, Xie R, Zhou L, Zhu J (2009) Dual-targeted antitumor effects against brainstem glioma by intravenous delivery of tumor necrosis factor-related, apoptosis-inducing, ligand-engineered human mesenchymal stem cells. Neurosurgery 65:610–624

    Article  PubMed  Google Scholar 

  • Yilmaz G, Granger DN (2010) Leukocyte recruitment and ischemic brain injury. Neuromolecular Med 12:193–204

    Article  PubMed  CAS  Google Scholar 

  • Yoo JY, Haseley A, Bratasz A, Chiocca EA, Zhang J, Powell K, Kaur B (2012) Antitumor efficacy of 34.5ENVE: a transcriptionally retargeted and “Vstat120”-expressing oncolytic virus. Mol Ther 20:287–297

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Natural Science Foundation of China, under contract (nos. 30901781, 81171131, 81172197, 30973079, and 81072056), and the doctoral start-up Foundation of Liaoning Province, no. 20091107.

Conflicts of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Shengjing Hospital, China Medical University, No.36, Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, People’s Republic of China

    Yi Hu & Yun-Hui Liu

  2. Department of Neurosurgery, the First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, 110004, People’s Republic of China

    Peng Cheng

  3. Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, 110004, People’s Republic of China

    Yi-Xue Xue

Authors
  1. Yi Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yi-Xue Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun-Hui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yun-Hui Liu.

Additional information

Yi Hu and Peng Cheng contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hu, Y., Cheng, P., Xue, YX. et al. Glioma Cells Promote the Expression of Vascular Cell Adhesion Molecule-1 on Bone Marrow-Derived Mesenchymal Stem Cells: a Possible Mechanism for Their Tropism Toward Gliomas. J Mol Neurosci 48, 127–135 (2012). https://doi.org/10.1007/s12031-012-9784-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-012-9784-7

Keywords

Search

Navigation