Clinical & Experimental Metastasis

, Volume 17, Issue 8, pp 669–676

Integrin α4β1/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma cells to hepatic sinusoidal endothelial cells under flow

  • Minas N.B. Papadimitriou
  • David G. Menter
  • Konstantinos Konstantopoulos
  • Garth L. Nicolson
  • Larry V. McIntire
Article

Abstract

Adhesion and stabilization of circulating tumor cells to endothelial cells in target blood vessels play an important role in the complex process of metastasis. We examined the cell surface receptors involved in the liver-metastatic adhesive interactions of murine RAW117 large-cell lymphoma cells to unstimulated hepatic sinusoidal endothelial cells (HSE) under physiological flow conditions. Flow cytometric analysis indicated that VCAM-1, ICAM-1 and PECAM-1 are constitutively expressed on the surfaces of both HSE and RAW117 cells. However, monoclonal antibody (mAb) blockade studies showed that ICAM-1 and PECAM-1 affected neither the attachment nor the stabilization step of the adhesion of RAW117 cells to HSE cell monolayers under flow. In contrast, RAW117 cells required a significantly lower shear stress to establish adhesion to HSE cells when VCAM-1 receptors on HSE cells were blocked with mAb. Furthermore, the presence of the anti-VCAM-1 mAb significantly decreased the extent of adhesion compared to that of the control, without affecting adherent cell stabilization times. Blocking the α4integrin subunits present mainly on RAW117 cells produced similar results to those previously observed with anti-VCAM-1 mAb. Although constitutively present mainly on the surfaces of RAW117 cells, MAdCAM-1 and β7 integrin subunit do not appear to play a role in either the arrest or stabilization of RAW117 cells on HSE cell monolayers. However, blocking the β1integrin subunit on the RAW117-H10 cells reduced adhesion to the same extent as anti-α4 and anti-VCAM-1 treatments. These observations suggest that an interaction of integrin α4β1on RAW117 cells with liver endothelial VCAM-1 occurs during the early stages of the adhesion process and may be important in liver metastasis.

alpha-4 integrins flow assay RAW117 cells tumor cell adhesion VCAM-1 

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References

  1. 1.
    Nicolson GL. Organ specificity of tumor metastasis: Role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 1988; 7(2): 143–88.PubMedCrossRefGoogle Scholar
  2. 2.
    Nicolson GL. Cancer metastasis: Tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim Biophys Acta 1988; 948(2): 175–224.PubMedGoogle Scholar
  3. 3.
    Auerbach R, Lu WC, Pardon E et al. Specificity of adhesion between murine tumor cells and capillary endothelium: An in vitro correlate of preferential metastasis in vivo. Cancer Res 1987; 47(6): 1492–6.PubMedGoogle Scholar
  4. 4.
    Nicolson GL, Winkelhake JL. Organ specificity of blood-born tumor metastasis determined by cell adhesion. Nature 1975; 255: 230–232.PubMedCrossRefGoogle Scholar
  5. 5.
    Nicolson GL, Belloni PN, Tressler RJ et al. Adhesive, invasive, and growth properties of selected metastatic variants of amurine large-cell lymphoma. Invasion Metastasis 1989; 9: 102–16.PubMedGoogle Scholar
  6. 6.
    Lafrenie RM, Buchanan MR, Orr FW. Adhesion molecules and their role in cancer metastasis. Cell Biophys 1993; 23: 3–89.PubMedGoogle Scholar
  7. 7.
    Tang DG, Honn KV. Adhesion molecules and tumor metastasis: An update. Invasion Metastasis 1994; 14: 109–22.PubMedGoogle Scholar
  8. 8.
    Vestweber D. Selectins: Cell surface lectins which mediate the binding of leukocytes to endothelial cells. Semin Cell Biol 1992; 3: 211–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Albelda SM. Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest 1993; 68: 4–17.PubMedGoogle Scholar
  10. 10.
    Gehlsen KR, Davis GE, Sriramarao P. Integrin expression in human melanoma cells with differing invasive and metastatic properties. Clin Exp Metastasis 1992; 10: 111–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Aoudjit F, Potworowski EF, Springer TA, St-Pierre Y. Protection from lymphoma cell metastasis in ICAM-1 mutant mice: A posthoming event. J Immunol 1998; 161: 2333–8.PubMedGoogle Scholar
  12. 12.
    Gude RP, Binda MM, Presas HL et al. Studies on the mechanisms responsible for inhibition of experimental metastasis of B16-F10 murine melanoma by pentoxifylline. J Biomed Sci 1999; 6: 133–41.PubMedGoogle Scholar
  13. 13.
    Fujii H, Inobe M, Hayakawa Y et al. Vaccination with B7–1+ tumor and anti-adhesion therapy with RGD pseudo-peptide (FC-336) efficiently induce anti-metastatic effect. Clin Exp Metastasis 1998; 16: 141–8.PubMedCrossRefGoogle Scholar
  14. 14.
    De Vita F, Infusino S, Auriemma A et al. Circulating levels of soluble intercellular adhesion molecule-1 in non-small cell lung cancer patients. Oncol Rep 1998; 5: 393–6.PubMedGoogle Scholar
  15. 15.
    Saiki I. Cell adhesion molecules and cancer metastasis. Jpn J Pharmacol 1997; 75: 215–42.PubMedGoogle Scholar
  16. 16.
    Brunson KW, Nicolson GL. Selection and biologic properties of malignant variants of a murine lymphosarcoma. J Natl Cancer Inst 1978; 61: 1499–503.PubMedGoogle Scholar
  17. 17.
    Belloni PN, Nicolson GL. Differential expression of cell surface glycoproteins on various organ-derived microvascular endothelia and endothelial cell cultures. J Cell Physiol 1988; 136: 398–410.PubMedCrossRefGoogle Scholar
  18. 18.
    Patton JT, Menter DG, Benson DM et al. Computerized analysis of tumor cells flowing in a parallel plate chamber to determine their adhesion stabilization lag time. Cell Motil Cytoskeleton (CRD) 1993; 26: 88–98.CrossRefGoogle Scholar
  19. 19.
    Belloni PN, Carney DH, Nicolson GL. Organ-derived microvessel endothelial cells exhibit differential responsiveness to thrombin and other growth factors. Microvasc Res 1992; 43(1): 20–45.PubMedCrossRefGoogle Scholar
  20. 20.
    Smith TW, Yun Z, Menter DG et al. Computerized analysis of tumor cell interactions with extracellular matrix proteins, peptides, and endothelial cells under laminar flow. Biotechnol Bioeng 1996; 50: 598–607.CrossRefPubMedGoogle Scholar
  21. 21.
    Koike C, Oku N, Watanabe M et al. Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties. Biochim Biophys Acta 1995; 1238(2): 99–106.PubMedCrossRefGoogle Scholar
  22. 22.
    Yun Z, Menter DG, Nicolson GL. Involvement of integrin alphavbeta3 in cell adhesion, motility, and liver metastasis of murine RAW117 large cell lymphoma. Cancer Res 1996; 56: 3103–11.PubMedGoogle Scholar
  23. 23.
    Chan BM, Elices MJ, Murphy E, Hemler ME. Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY. J Biol Chem 1992; 267: 8366–70.PubMedGoogle Scholar
  24. 24.
    Postigo AA, Sanchez-Mateos P, Lazarovits AI et al. Alpha 4 beta 7 integrin mediates B cell binding to fibronectin and vascular cell adhesion molecule-1. Expression and function of alpha 4 integrins on human B lymphocytes. J Immunol 1993; 151: 2471–83.PubMedGoogle Scholar
  25. 25.
    Berlin C, Berg EL, Briskin MJ et al. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 1993; 74: 185–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Erle DJ, Briskin MJ, Butcher EC et al. Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. J Immunol 1994; 153: 517–28.PubMedGoogle Scholar
  27. 27.
    Patrick CW, Jr., Smith TW, McIntire LV, Juneja HS. Cellular interactions among marrow stromal and normal/neoplastic pre-B-and B-lymphoblastic cells. Leuk Lymph 1996; 22: 205–19.Google Scholar
  28. 28.
    Konstantopoulos K, Kukreti S, Smith CW, McIntire LV. Endothelial P-selectin and VCAM-1 each can function as primary adhesive mechanisms for T cells under conditions of flow. J Leuk Biol 1997; 61: 179–87.Google Scholar
  29. 29.
    Jacobsen K, Kravitz J, Kincade PW, Osmond DG. Adhesion receptors on bone marrow stromal cells: In vivo expression of vascular cell adhesion molecule-1 by reticular cells and sinusoidal endothelium in normal and gamma-irradiated mice. Blood 1996; 87: 73–82.PubMedGoogle Scholar
  30. 30.
    Garcia-Barcina M, Lukomska B, Gawron W et al. Expression of cell adhesion molecules on liver-associated lymphocytes and their ligands on sinusoidal lining cells in patients with benign or malignant liver disease. Am J Pathol 1995; 146: 1406–13.PubMedGoogle Scholar
  31. 31.
    Martin-Padura I, Mortarini R, Lauri D et al. Heterogeneity in human melanoma cell adhesion to cytokine activated endothelial cells correlates with VLA-4 expression. Cancer Res 1991; 51: 2239–41.PubMedGoogle Scholar
  32. 32.
    Giavazzi R, Foppolo M, Dossi R, Remuzzi A. Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions. J Clin Invest 1993; 92: 3038–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Taichman DB, Cybulsky MI, Djaffar I et al. Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1. Cell Regul 1991; 2(5): 347–55.PubMedGoogle Scholar
  34. 34.
    Norton J, al-Saffar N, Sloane JP. Adhesion molecule expression in human hepatic graft-versus-host disease. Bone Marrow Transplant. 1992; 10: 153–6.PubMedGoogle Scholar
  35. 35.
    Ohteki T, Okamoto S, Nakamura M et al. Elevated production of interleukin 6 by hepatic MNC correlates with ICAM-1 expression on the hepatic sinusoidal endothelial cells in autoimmune MRL/lpr mice. Immunol Lett 1993; 36: 145–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Couvelard A, Scoazec JY, Feldmann G. Expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in the normal and cirrhotic human liver. Am J Pathol 1993; 143: 738–52.PubMedGoogle Scholar
  37. 37.
    Tang DG, Chen YQ, Newman PJ et al. Identification of PECAM-1 in solid tumor cells and its potential involvement in tumor cell adhesion to endothelium. J Biol Chem 1993; 268: 22883–94.PubMedGoogle Scholar
  38. 38.
    Yun Z, Smith TW, Menter DG et al. Differential adhesion of metastatic RAW117 large-cell lymphoma cells under static or hydrodynamic conditions: role of integrin alpha(v) beta3. Clin Exp Metastasis 1997; 15: 3–11.PubMedCrossRefGoogle Scholar
  39. 39.
    Koike C, Watanabe M, Oku N et al. Tumor cells with organ-specific metastatic ability show distinctive trafficking in vivo: Analyses by positron emission tomography and bioimaging. Cancer Res 1997; 57: 3612–9.PubMedGoogle Scholar
  40. 40.
    Kikkawa H, Miyamoto D, Imafuku H et al. Role of sialylglycoconjugate( s) in the initial phase of metastasis of liver-metastatic RAW117 lymphoma cells. Jpn J Cancer Res 1998; 89: 1296–305.PubMedGoogle Scholar
  41. 41.
    Nicolson GL. Tumor and host molecules important in the organ preference of metastasis. Semin Cancer Biol 1991; 2: 143–54.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Minas N.B. Papadimitriou
    • 1
  • David G. Menter
    • 2
  • Konstantinos Konstantopoulos
    • 1
  • Garth L. Nicolson
    • 3
  • Larry V. McIntire
    • 1
  1. 1.Cox Laboratory for Biomedical Engineering, Institute of Biosciences and Bioengineering –Rice UniversityHoustonUSA
  2. 2.Department of Clinical Cancer PreventionThe University of TexasHoustonUSA
  3. 3.Institute for Molecular MedicineUSA

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