Skip to main content

Advertisement

Log in

Role of the β1-integrin subunit in the adhesion, extravasation and migration of T24 human bladder carcinoma cells

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell–cell and cell–matrix interactions. We investigated the role of integrin subunits in the adhesion, extravasation and migration of the highly invasive human bladder carcinoma cell line T24. Here we show that inhibition of the β1-integrin subunit using the specific β1-integrin blocking antibody 4B4 significantly reduces the adhesion to HUVEC and transmigratory activity of T24 cells. The blockade of the β1-integrin subunit also resulted in a significantly reduced locomotory activity of T24 cells. A detailed cell migration analysis on a single cell level revealed that blockade of the β1-integrin subunit leads to an altered migration pattern of single cells but does not influence migration per se. Migration parameters such as time active, velocity and distance migrated were significantly reduced as compared to untreated control cells. Our observations strongly suggest a central role for the β1-integrin subunit in forming the cell–cell and cell–matrix bonds necessary for adhesion, extravasation and migration.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

FCS:

fetal calf serum

HUVEC:

human umbilical vein endothelial cell

IL-8:

Interleukin-8

XTT:

(2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tretrazolium-5-carboxanilide) sodium salt

References

  1. T Dittmar A Husemann Y Schewe et al. (2002) ArticleTitleInduction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c-erbB-2 receptor via EGFR FASEB J 16 IssueID13 1823–5 Occurrence Handle12354693

    PubMed  Google Scholar 

  2. J Haier T Korb B Hotz et al. (2003) ArticleTitleAn intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation J Gastrointest Surg 7 IssueID4 507–14 Occurrence Handle10.1016/S1091-255X(03)00023-4 Occurrence Handle12763408

    Article  PubMed  Google Scholar 

  3. C Heyder E Gloria-Maercker F Entschladen et al. (2002) ArticleTitleRealtime visualization of tumor cell/endothelial cell interactions during transmigration across the endothelial barrier J Cancer Res Clin Oncol 128 IssueID10 533–8 Occurrence Handle10.1007/s00432-002-0377-7 Occurrence Handle12384796

    Article  PubMed  Google Scholar 

  4. R Engers HE. Gabbert (2000) ArticleTitleMechanisms of tumor metastasis: Cell biological aspects and clinical implications J Cancer Res Clin Oncol 126 IssueID12 682–92 Occurrence Handle10.1007/s004320000148 Occurrence Handle11153140

    Article  PubMed  Google Scholar 

  5. FG. Giancotti (2000) ArticleTitleComplexity and specificity of integrin signalling Nat Cell Biol 2 IssueID1 E13–4 Occurrence Handle10.1038/71397 Occurrence Handle10620816

    Article  PubMed  Google Scholar 

  6. CM Longhurst LK. Jennings (1998) ArticleTitleIntegrin-mediated signal transduction Cell Mol Life Sci 54 IssueID6 514–26 Occurrence Handle10.1007/s000180050180 Occurrence Handle9676571

    Article  PubMed  Google Scholar 

  7. AE Aplin A Howe SK Alahari et al. (1998) ArticleTitleSignal transduction and signal modulation by cell adhesion receptors: The role of integrins, cadherins, immunoglobulin-cell adhesion molecules, and selectins Pharmacol Rev 50 IssueID2 197–263 Occurrence Handle9647866

    PubMed  Google Scholar 

  8. DL Crowe CF. Shuler (1999) ArticleTitleRegulation of tumor cell invasion by extracellular matrix Histol Histopathol 14 IssueID2 665–71 Occurrence Handle10212827

    PubMed  Google Scholar 

  9. DG Tang KV. Honn (1994) ArticleTitleAdhesion molecules and tumor metastasis: An update Invas Metast 14 IssueID1–6 109–22

    Google Scholar 

  10. J Pilch R Habermann B. Felding-Habermann (2002) ArticleTitleUnique ability of integrin alpha(v)beta 3 to support tumor cell arrest under dynamic flow conditions J Biol Chem 277 IssueID24 21930–8 Occurrence Handle10.1074/jbc.M201630200 Occurrence Handle11934894

    Article  PubMed  Google Scholar 

  11. EB Voura RA Ramjeesingh AM Montgomery et al. (2001) ArticleTitleInvolvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells Mol Biol Cell 12 IssueID9 2699–710 Occurrence Handle11553709

    PubMed  Google Scholar 

  12. AR Cardones T Murakami ST. Hwang (2003) ArticleTitleCXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin Cancer Res 63 IssueID20 6751–7 Occurrence Handle14583470

    PubMed  Google Scholar 

  13. LC Plantefaber RO. Hynes (1989) ArticleTitleChanges in integrin receptors on oncogenically transformed cells Cell 56 IssueID2 281–90 Occurrence Handle10.1016/0092-8674(89)90902-1 Occurrence Handle2521461

    Article  PubMed  Google Scholar 

  14. S Fujita H Suzuki M Kinoshita et al. (1992) ArticleTitleInhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin beta 1 subunit antibody Jpn J Cancer Res 83 IssueID12 1317–26 Occurrence Handle1282908

    PubMed  Google Scholar 

  15. T Tsuji Y Kawada M Kai-Murozono et al. (2002) ArticleTitleRegulation of melanoma cell migration and invasion by laminin-5 and alpha3beta1 integrin (VLA-3) Clin Exp Metast 19 IssueID2 127–34 Occurrence Handle10.1023/A:1014573204062

    Article  Google Scholar 

  16. D Hangan VL Morris L Boeters et al. (1997) ArticleTitleAn epitope on VLA-6 (alpha6beta1) integrin involved in migration but not adhesion is required for extravasation of murine melanoma B16F1 cells in liver Cancer Res 57 IssueID17 3812–7 Occurrence Handle9288792

    PubMed  Google Scholar 

  17. NJ Tawil V Gowri M Djoneidi et al. (1996) ArticleTitleIntegrin alpha3beta1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma Int J Cancer 66 IssueID5 703–10 Occurrence Handle10.1002/(SICI)1097-0215(19960529)66:5<703::AID-IJC20>3.0.CO;2-3 Occurrence Handle8647636

    Article  PubMed  Google Scholar 

  18. EJ Andrews JH Wang DC Winter et al. (2001) ArticleTitleTumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression J Surg Res 97 IssueID1 14–9 Occurrence Handle10.1006/jsre.2001.6090 Occurrence Handle11319874

    Article  PubMed  Google Scholar 

  19. T Saito M Kimura T Kawasaki et al. (1996) ArticleTitleCorrelation between integrin alpha 5 expression and the malignant phenotype of transitional cell carcinoma Br J Cancer 73 IssueID3 327–31

    Google Scholar 

  20. P Laidler D Gil A Pituch-Noworolska et al. (2000) ArticleTitleExpression of beta1-integrins and N-cadherin in bladder cancer and melanoma cell lines Acta Biochim Pol 47 IssueID4 1159–70 Occurrence Handle11996105

    PubMed  Google Scholar 

  21. A Litynska M Przybylo E Pochec et al. (2002) ArticleTitleAdhesion properties of human bladder cell lines with extracellular matrix components: The role of integrins and glycosylation Acta Biochim Pol 49 IssueID3 643–50 Occurrence Handle12422234

    PubMed  Google Scholar 

  22. T Dittmar F Schafer BH Brandt et al. (2000) ArticleTitleAccelerated assessing of antisense RNA efficacy using a chimeric enhanced green fluorescent protein-antisense RNA-producing vector Antisense Nucleic-Acid Drug Dev 10 IssueID5 401–8 Occurrence Handle11079579

    PubMed  Google Scholar 

  23. Y Katterle BH Brandt SF Dowdy et al. (2004) ArticleTitleAntitumour effects of PLC-gamma1-(SH2)(2)-TAT fusion proteins on EGFR/c-erbB-2-positive breast cancer cells Br J Cancer 90 IssueID1 230–5

    Google Scholar 

  24. C Weidt B Niggemann W Hatzmann et al. (2004) ArticleTitleDifferential effects of culture conditions on the migration pattern of stromal cell-derived factor-stimulated hematopoietic stem cells Stem Cells 22 IssueID6 890–6 Occurrence Handle10.1634/stemcells.22-6-890 Occurrence Handle15536181

    Article  PubMed  Google Scholar 

  25. B Niggemann TL Drell J Joseph et al. (2004) ArticleTitleTumor cell locomotion: Differential dynamics of spontaneous and induced migration in a 3D collagen matrix Exp Cell Res 298 IssueID1 178–87 Occurrence Handle10.1016/j.yexcr.2004.04.001 Occurrence Handle15242772

    Article  PubMed  Google Scholar 

  26. C Morimoto NL Letvin AW. Boyd (1985) ArticleTitleThe isolation and characterization of the human helper inducer T cell subset J Immunol 134 IssueID6 3762–9 Occurrence Handle3157750

    PubMed  Google Scholar 

  27. WG Carter EA Wayner TS Bouchard et al. (1990) ArticleTitleThe role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells J Cell Biol 110 IssueID4 1387–404 Occurrence Handle10.1083/jcb.110.4.1387 Occurrence Handle1691191

    Article  PubMed  Google Scholar 

  28. E Rubinstein F Le Naour C Lagaudriere-Gesbert et al. (1996) ArticleTitleCD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins Eur J Immunol 26 IssueID11 2657–65 Occurrence Handle8921952

    PubMed  Google Scholar 

  29. M Lehmann C Rabenandrasana R Tamura et al. (1994) ArticleTitleA monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon carcinoma cell line and recognizes the integrins alpha v beta 3, alpha v beta 5, and alpha v beta 6 Cancer Res 54 IssueID8 2102–7 Occurrence Handle7513610

    PubMed  Google Scholar 

  30. BA Kallmann S Wagner V Hummel et al. (2002) ArticleTitleCharacteristic gene expression profile of primary human cerebral endothelial cells FASEB J 16 IssueID6 589–91 Occurrence Handle11919163

    PubMed  Google Scholar 

  31. H Tachimoto M Ebisawa BS. Bochner (2002) ArticleTitleCross-talk between integrins and chemokines that influences eosinophil adhesion and migration Int Arch Allergy Immunol 128 IssueIDSuppl 1 18–20 Occurrence Handle10.1159/000059414 Occurrence Handle12065905

    Article  PubMed  Google Scholar 

  32. RS. Ross (2004) ArticleTitleMolecular and mechanical synergy: Cross-talk between integrins and growth factor receptors Cardiovasc Res 63 IssueID3 381–90 Occurrence Handle10.1016/j.cardiores.2004.04.027 Occurrence Handle15276463

    Article  PubMed  Google Scholar 

  33. SD Blystone FP Lindberg SE LaFlamme et al. (1995) ArticleTitleIntegrin beta 3 cytoplasmic tail is necessary and sufficient for regulation of alpha 5 beta 1 phagocytosis by alpha v beta 3 and integrin-associated protein J Cell Biol 130 IssueID3 745–54 Occurrence Handle10.1083/jcb.130.3.745 Occurrence Handle7542659

    Article  PubMed  Google Scholar 

  34. JS Bauer CL Schreiner FG Giancotti et al. (1992) ArticleTitleMotility of fibronectin receptor-deficient cells on fibronectin and vitronectin: Collaborative interactions among integrins J Cell Biol 116 IssueID2 477–87 Occurrence Handle10.1083/jcb.116.2.477 Occurrence Handle1370495

    Article  PubMed  Google Scholar 

  35. A Dorfleutner E Hintermann T Tarui et al. (2004) ArticleTitleCross-talk of integrin alpha3beta1 and tissue factor in cell migration Mol Biol Cell 15 IssueID10 4416–25 Occurrence Handle10.1091/mbc.E03-09-0640 Occurrence Handle15254262

    Article  PubMed  Google Scholar 

  36. JF Marshall IR. Hart (1996) ArticleTitleThe role of alpha v-integrins in tumour progression and metastasis Semin Cancer Biol 7 IssueID3 129–38 Occurrence Handle10.1006/scbi.1996.0018 Occurrence Handle8773298

    Article  PubMed  Google Scholar 

  37. NC Wong BM Mueller CF Barbas et al. (1998) ArticleTitleAlpha v-integrins mediate adhesion and migration of breast carcinoma cell lines Clin Exp Metast 16 IssueID1 50–61 Occurrence Handle10.1023/A:1006512018609

    Article  Google Scholar 

  38. T Sato K Konishi K Maeda et al. (2003) ArticleTitleIntegrin alpha v, c-erbB2 and DNA ploidy in lung metastases from colorectal cancer Hepatogastroenterology 50 IssueID49 27–30 Occurrence Handle12629984

    PubMed  Google Scholar 

  39. P Koistinen M Ahonen VM Kahari et al. (2004) ArticleTitlealphaV integrin promotes in vitro and in vivo survival of cells in metastatic melanoma Int J Cancer 112 IssueID1 61–70 Occurrence Handle10.1002/ijc.20377 Occurrence Handle15305376

    Article  PubMed  Google Scholar 

  40. AR Whitney M Diehn SJ Popper et al. (2003) ArticleTitleIndividuality and variation in gene expression patterns in human blood Proc Natl Acad Sci USA 100 IssueID4 1896–901 Occurrence Handle10.1073/pnas.252784499 Occurrence Handle12578971

    Article  PubMed  Google Scholar 

  41. F Monier-Gavelle JL. Duband (1997) ArticleTitleCross talk between adhesion molecules: Control of N-cadherin activity by intracellular signals elicited by beta1 and beta3 integrins in migrating neural crest cells J Cell Biol 137 IssueID7 1663–81 Occurrence Handle10.1083/jcb.137.7.1663 Occurrence Handle9199179

    Article  PubMed  Google Scholar 

  42. U. Cavallaro (2004) ArticleTitleN-cadherin as an invasion promoter: A novel target for antitumor therapy? Curr Opin Investig Drugs 5 IssueID12 1274–8 Occurrence Handle15648948

    PubMed  Google Scholar 

  43. Y Jia ZZ Zeng SM Markwart et al. (2004) ArticleTitleIntegrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells Cancer Res 64 IssueID23 8674–81 Occurrence Handle15574776

    PubMed  Google Scholar 

  44. SM Ellerbroek DA Fishman AS Kearns et al. (1999) ArticleTitleOvarian carcinoma regulation of matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase through beta1 integrin Cancer Res 59 IssueID7 1635–41 Occurrence Handle10197640

    PubMed  Google Scholar 

  45. SO Yoon SJ Park CH Yun et al. (2003) ArticleTitleRoles of matrix metalloproteinases in tumor metastasis and angiogenesis J Biochem Mol Biol 36 IssueID1 128–37 Occurrence Handle12542983

    PubMed  Google Scholar 

  46. K Lang B Niggemann KS Zanker et al. (2002) ArticleTitleSignal processing in migrating T24 human bladder carcinoma cells: Role of the autocrine interleukin-8 loop Int J Cancer 99 IssueID5 673–80 Occurrence Handle10.1002/ijc.10424 Occurrence Handle12115500

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas Dittmar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heyder, C., Gloria-Maercker, E., Hatzmann, W. et al. Role of the β1-integrin subunit in the adhesion, extravasation and migration of T24 human bladder carcinoma cells. Clin Exp Metastasis 22, 99–106 (2005). https://doi.org/10.1007/s10585-005-4335-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-005-4335-z

Keywords

Navigation