Association of α v β 3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells (original) (raw)

Abstract

Introduction. Expression of adhesion molecules such as α v β 3 integrin has been associated with the metastatic potential of tumor cells. The purpose of this study was to determine whether α v β 3 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 β 3 integrin expression using flow cytometry. Results. α v β 3 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 β 3. 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 β 3 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 β 3 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 β 3 integrin may therefore be a potential new target for osteosarcoma.

Access this article

Log in via an institution

Subscribe and save

Buy Now

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

BSA:

bovine serum albumin

EC:

endothelial cell

FBS:

fetal bovine serum

OS:

osteosarcoma

PBS:

phosphate-buffered saline

VN:

vitronectin

References

  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; 1600–6
  2. B Felding-Habermann E Fransvea TE O’Toole_et al._ (2002)ArticleTitleInvolvement of tumor cell integrin α v β3 in hematogenous metastasis of human melanoma cells_Clinical & Experimental Metastasis_ 19 427–36
    Google Scholar
  3. RO. Hynes (1992)ArticleTitleIntegrins: Versatility, modulation, and signaling in cell adhesion_Clinical & Experimental Metastasis_ 69 11–25
    Google Scholar
  4. L Scheibler DF Mierke G Bitan_et al._ (2001)ArticleTitleIdentification of a contact domain between echistatin and the integrin α v β3 by photoaffinity cross-linking_Clinical & Experimental Metastasis_ 40 15117–26
    Google Scholar
  5. B Felding-Habermann TE O’Toole JW Smith_et al._ (2001)ArticleTitleIntegrin activation controls metastasis in human breast cancer_Clinical & Experimental Metastasis_ 98 1853–8
    Google Scholar
  6. TG Hullinger LK McCauley ML Dejoode_et al._ (1998)ArticleTitleEffect of bone marrow endothelial cell line_Clinical & Experimental Metastasis_ 36 14–22
    Google Scholar
  7. M Platten W Wick C Wild-Bode_et al._ (2000)ArticleTitleTransforming growth factors β1 (TGF-β1) and TGF-β2 promote glioma cell migration via up-regulation of α v β3 integrin expression_Clinical & Experimental Metastasis_ 268 607–11
    Google Scholar
  8. N Reinmuth W Liu SA Ahmak_et al._ (2003)ArticleTitle α v β 3 Integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival in mice_Clinical & Experimental Metastasis_ 63 2079–87
    Google Scholar
  9. A Vonlaufen G Wiedle B Borisch_et al._ (2001)ArticleTitleIntegrin α v β3 expression in colon carcinoma correlates with survival_Clinical & Experimental Metastasis_ 14 IssueID11 1126–32
    Google Scholar
  10. SF Jia LL Worth ES. Kleinerman (1999)ArticleTitleA nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies_Clinical & Experimental Metastasis_ 17 501–6
    Google Scholar
  11. RR Langley KM Ramirez RZ Tsan_et al._ (2003)ArticleTitleTissue-specific microvascular endothelial cell lines from H-2Kb-tsA58 mice for studies of angiogenesis and metastasis_Clinical & Experimental Metastasis_ 63 2971–6
    Google Scholar
  12. K Minamiguchi H Kumagai T Masuda_et al._ (2001)ArticleTitleThiolutin, an inhibitor of HUVEC adhesion to vitronectin, reduces paxillin in HUVECs and suppresses tumor cell-induced angiogenesis_Clinical & Experimental Metastasis_ 93 307–16
    Google Scholar
  13. R Faccio M Grano S Colucci_et al._ (2002)ArticleTitleLocalization and possible role of two different alpha v beta 3 integrin conformations in resting and resorbing osteoclasts_Clinical & Experimental Metastasis_ 115 2919–29
    Google Scholar
  14. EB Voura RA Ramjeesingh AMP Montgomery_et al._ (2001)ArticleTitleInvolvement of integrin α v β 3 and cell adhesion molecule L1 in transendothelial migration of melanoma cells_Clinical & Experimental Metastasis_ 12 2699–710
    Google Scholar
  15. EI Deryugina MA Bourdon K Jungwirth_et al._ (2000)ArticleTitleFunctional activation of integrin α v β3 in tumor cells expressing membrane-type 1 matrix metalloproteinase_Clinical & Experimental Metastasis_ 86 15–23
    Google Scholar
  16. W Stetler-Stevenson S Aznavoorian L. Liotta (1993)ArticleTitleTumor cell interactions with the extracellular matrix during invasion and metastasis_Clinical & Experimental Metastasis_ 9 541–73
    Google Scholar
  17. FW Orr HH Wang RM Lafrenie_et al._ (2000)ArticleTitleInteractions between cancer cells and the endothelium in metastasis_Clinical & Experimental Metastasis_ 190 310–29
    Google Scholar
  18. IR Hart M Birch JF. Marshall (1991)ArticleTitleCell adhesion receptor expression during melanoma progression and metastasis_Clinical & Experimental Metastasis_ 10 115–28
    Google Scholar
  19. IJ. Fidler (2001)ArticleTitleSeed and soil revisited_Clinical & Experimental Metastasis_ 10 257–69
    Google Scholar
  20. S Curran GI. Murray (1999)ArticleTitleMatrix metalloproteinases in tumor invasion and metastasis_Clinical & Experimental Metastasis_ 189 300–8
    Google Scholar
  21. CC Kumar M Malkowski Z Yin_et al._ (2001)ArticleTitleInhibition of angiogenesis and tumor growth by SCH221153, a dual α v β2 and α v β5 integrin receptor antagonist_Clinical & Experimental Metastasis_ 61 2232–8
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 87, Houston, TX, 77030, USA
    Xiaoping Duan, Shu-Fang Jia, Zhichao Zhou, Marcela F. Bolontrade & Eugenie S. Kleinerman
  2. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
    Robert R. Langley & Eugenie S. Kleinerman

Authors

  1. Xiaoping Duan
    You can also search for this author inPubMed Google Scholar
  2. Shu-Fang Jia
    You can also search for this author inPubMed Google Scholar
  3. Zhichao Zhou
    You can also search for this author inPubMed Google Scholar
  4. Robert R. Langley
    You can also search for this author inPubMed Google Scholar
  5. Marcela F. Bolontrade
    You can also search for this author inPubMed Google Scholar
  6. Eugenie S. Kleinerman
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toEugenie S. Kleinerman.

Rights and permissions

About this article

Cite this article

Duan, X., Jia, SF., Zhou, Z. et al. Association of α v β 3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells.Clin Exp Metastasis 21, 747–753 (2005). https://doi.org/10.1007/s10585-005-0599-6

Download citation

Keywords