Advertisement

Clinical & Experimental Metastasis

, Volume 21, Issue 8, pp 747–753 | Cite as

Association of α v β3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells

  • Xiaoping Duan
  • Shu-Fang Jia
  • Zhichao Zhou
  • Robert R. Langley
  • Marcela F. Bolontrade
  • Eugenie S. Kleinerman
Article

Abstract

Introduction. Expression of adhesion molecules such as α v β3 integrin has been associated with the metastatic potential of tumor cells. The purpose of this study was to determine whether α v β3 expression correlated with the metastatic potential of human osteosarcoma cells. Materials and methods. We developed a series of sublines (LM2–LM7) from human osteosarcoma SAOS parental cells, with progressively increasing potential to form lung metastases in nude mice after intravenous injection. SAOS parental and LM2 cells were poorly metastatic, but LM7 cells resulted in visible metastatic lung nodules by 6–8 weeks. We quantified α v β3 integrin expression using flow cytometry. Results. α v β3 expression correlated with the metastatic potential of the cells, with LM7 cells showing the highest expression. LM7 cell adhesion to vitronectin decreased after treatment with echistatin, a RGD-containing peptide antagonist of α v β3. LM7 cells demonstrated higher chemotactic activity than SAOS cells to a homogenate made from lung tissue. This chemotactic activity was also inhibited by echistatin. These data indicated that α v β3 was critical for the migration of LM7 cells to the lung homogenate. Chemotaxis to a liver homogenate was the same for LM7 and SAOS cells. Migration of LM7 cells through lung endothelial cells was higher than that through liver endothelial cells, and echistatin again inhibited this migration. Conclusions. α v β3 integrin expression may play a role in the metastatic potential of osteosarcoma cells by enhancing the ability of the cells to migrate specifically to the lung. α v β3 integrin may therefore be a potential new target for osteosarcoma.

Keywords

αvβ3 integrin metastasis migration osteosarcoma 

Abbreviations

BSA

bovine serum albumin

EC

endothelial cell

FBS

fetal bovine serum

OS

osteosarcoma

PBS

phosphate-buffered saline

VN

vitronectin

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Link MP, Goorin AM, Miser AW et al. The effect of adjuvant therapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med 1986; 1600–6Google Scholar
  2. 2.
    Felding-Habermann, B, Fransvea, E, O’Toole, TE,  et al. 2002Involvement of tumor cell integrin α v β3 in hematogenous metastasis of human melanoma cellsClinical & Experimental Metastasis1942736Google Scholar
  3. 3.
    Hynes, RO. 1992Integrins: Versatility, modulation, and signaling in cell adhesionClinical & Experimental Metastasis691125Google Scholar
  4. 4.
    Scheibler, L, Mierke, DF, Bitan, G,  et al. 2001Identification of a contact domain between echistatin and the integrin α v β3 by photoaffinity cross-linkingClinical & Experimental Metastasis401511726Google Scholar
  5. 5.
    Felding-Habermann, B, O’Toole, TE, Smith, JW,  et al. 2001Integrin activation controls metastasis in human breast cancerClinical & Experimental Metastasis9818538Google Scholar
  6. 6.
    Hullinger, TG, McCauley, LK, Dejoode, ML,  et al. 1998Effect of bone marrow endothelial cell lineClinical & Experimental Metastasis361422Google Scholar
  7. 7.
    Platten, M, Wick, W, Wild-Bode, C,  et al. 2000Transforming growth factors β1 (TGF-β1) and TGF-β2 promote glioma cell migration via up-regulation of α v β3 integrin expressionClinical & Experimental Metastasis26860711Google Scholar
  8. 8.
    Reinmuth, N, Liu, W, Ahmak, SA,  et al. 2003α v β3 Integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival in miceClinical & Experimental Metastasis63207987Google Scholar
  9. 9.
    Vonlaufen, A, Wiedle, G, Borisch, B,  et al. 2001Integrin α v β3 expression in colon carcinoma correlates with survivalClinical & Experimental Metastasis14112632Google Scholar
  10. 10.
    Jia, SF, Worth, LL, Kleinerman, ES. 1999A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategiesClinical & Experimental Metastasis175016Google Scholar
  11. 11.
    Langley, RR, Ramirez, KM, Tsan, RZ,  et al. 2003Tissue-specific microvascular endothelial cell lines from H-2Kb-tsA58 mice for studies of angiogenesis and metastasisClinical & Experimental Metastasis6329716Google Scholar
  12. 12.
    Minamiguchi, K, Kumagai, H, Masuda, T,  et al. 2001Thiolutin, an inhibitor of HUVEC adhesion to vitronectin, reduces paxillin in HUVECs and suppresses tumor cell-induced angiogenesisClinical & Experimental Metastasis9330716Google Scholar
  13. 13.
    Faccio, R, Grano, M, Colucci, S,  et al. 2002Localization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclastsClinical & Experimental Metastasis115291929Google Scholar
  14. 14.
    Voura, EB, Ramjeesingh, RA, Montgomery, AMP,  et al. 2001Involvement of integrin α v β3 and cell adhesion molecule L1 in transendothelial migration of melanoma cellsClinical & Experimental Metastasis122699710Google Scholar
  15. 15.
    Deryugina, EI, Bourdon, MA, Jungwirth, K,  et al. 2000Functional activation of integrin α v β3 in tumor cells expressing membrane-type 1 matrix metalloproteinaseClinical & Experimental Metastasis861523Google Scholar
  16. 16.
    Stetler-Stevenson, W, Aznavoorian, S, Liotta, L. 1993Tumor cell interactions with the extracellular matrix during invasion and metastasisClinical & Experimental Metastasis954173Google Scholar
  17. 17.
    Orr, FW, Wang, HH, Lafrenie, RM,  et al. 2000Interactions between cancer cells and the endothelium in metastasisClinical & Experimental Metastasis19031029Google Scholar
  18. 18.
    Hart, IR, Birch, M, Marshall, JF. 1991Cell adhesion receptor expression during melanoma progression and metastasisClinical & Experimental Metastasis1011528Google Scholar
  19. 19.
    Fidler, IJ. 2001Seed and soil revisitedClinical & Experimental Metastasis1025769Google Scholar
  20. 20.
    Curran, S, Murray, GI. 1999Matrix metalloproteinases in tumor invasion and metastasisClinical & Experimental Metastasis1893008Google Scholar
  21. 21.
    Kumar, CC, Malkowski, M, Yin, Z,  et al. 2001Inhibition of angiogenesis and tumor growth by SCH221153, a dual α v β2 and α v β5 integrin receptor antagonistClinical & Experimental Metastasis6122328Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Xiaoping Duan
    • 1
  • Shu-Fang Jia
    • 1
  • Zhichao Zhou
    • 1
  • Robert R. Langley
    • 2
  • Marcela F. Bolontrade
    • 1
  • Eugenie S. Kleinerman
    • 1
    • 2
  1. 1.Division of PediatricsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Cancer BiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations