Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Nov;68(5):862–867. doi: 10.1038/bjc.1993.446

Decreased adhesion to endothelial cells and matrix proteins of H-2Kb gene transfected tumour cells.

D Lauri 1, C De Giovanni 1, T Biondelli 1, E Lalli 1, L Landuzzi 1, A Facchini 1, G Nicoletti 1, P Nanni 1, E Dejana 1, P L Lollini 1
PMCID: PMC1968745  PMID: 7692918

Abstract

Transfection of murine metastatic B78H1 cells (derived from B16 melanoma) with a syngeneic H-2Kb gene was used to study the effect of Major Histocompatibility Complex (MHC) gene products on tumour cell adhesion to endothelial cells and matrix proteins and the involvement in the metastatic process. H-2Kb-expressing transfectants showed a reduced adhesion to endothelial surfaces of different origin (four murine endotheliomas and human umbilical vein endothelial cells) when compared to parental B78H1 cells and to controls transfected with pSV2neo alone. On the average a 50-70% reduction in adhesion to endothelial cells was observed among H-2Kb transfectants. H-2Kb transfectants had a reduced expression of the alpha 4 integrin subunit, moreover the adhesion of Neo-transfected clones to endothelial cells was reduced to the levels of H-2Kb transfectants by antibodies directed against the beta 1 subunit and the endothelial VCAM-1 molecule, thus suggesting an impairment of the VLA-4/VCAM-1 interaction in H-2Kb transfectants. Adhesion to extracellular matrix components was also strongly decreased: in general the adhesion of H-2Kb cells showed a 50-75% inhibition with respect to Neo or parental controls. The highest difference was observed in adhesion to vitronectin and laminin, the lowest in adhesion to fibronectin. Reduction in adhesive properties of H-2Kb-expressing transfectants could be involved in the reduced metastatic ability, evaluated by means of intravenous injection of cells: H-2Kb transfectants yielded less than ten lung colonies, while all controls produced more than 100. Our data indicate that expression of a single class I MHC gene can significantly alter the metastatic phenotype of MHC-negative tumour cells and this could be related to a general alteration of tumour cell adhesive interactions.

Full text

PDF
862

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M., Mette S. A., Elder D. E., Stewart R., Damjanovich L., Herlyn M., Buck C. A. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990 Oct 15;50(20):6757–6764. [PubMed] [Google Scholar]
  2. Auerbach R., Lu W. C., Pardon E., Gumkowski F., Kaminska G., Kaminski M. Specificity of adhesion between murine tumor cells and capillary endothelium: an in vitro correlate of preferential metastasis in vivo. Cancer Res. 1987 Mar 15;47(6):1492–1496. [PubMed] [Google Scholar]
  3. Balconi G., Dejana E. Cultivation of endothelial cells: limitations and perspectives. Med Biol. 1986;64(5):231–245. [PubMed] [Google Scholar]
  4. Bartlett P. F., Edidin M. Effect of the H-2 gene complex rates of fibroblast intercellular adhesion. J Cell Biol. 1978 May;77(2):377–388. doi: 10.1083/jcb.77.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Belloni P. N., Tressler R. J. Microvascular endothelial cell heterogeneity: interactions with leukocytes and tumor cells. Cancer Metastasis Rev. 1990 Feb;8(4):353–389. doi: 10.1007/BF00052608. [DOI] [PubMed] [Google Scholar]
  6. Carlos T. M., Schwartz B. R., Kovach N. L., Yee E., Rosa M., Osborn L., Chi-Rosso G., Newman B., Lobb R., Rosso M. Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. Blood. 1990 Sep 1;76(5):965–970. [PubMed] [Google Scholar]
  7. Chang Y. S., Chen Y. Q., Timar J., Nelson K. K., Grossi I. M., Fitzgerald L. A., Diglio C. A., Honn K. V. Increased expression of alpha IIb beta 3 integrin in subpopulations of murine melanoma cells with high lung-colonizing ability. Int J Cancer. 1992 May 28;51(3):445–451. doi: 10.1002/ijc.2910510318. [DOI] [PubMed] [Google Scholar]
  8. Conforti G., Zanetti A., Colella S., Abbadini M., Marchisio P. C., Pytela R., Giancotti F., Tarone G., Languino L. R., Dejana E. Interaction of fibronectin with cultured human endothelial cells: characterization of the specific receptor. Blood. 1989 May 1;73(6):1576–1585. [PubMed] [Google Scholar]
  9. Curtis A. S., Rooney P. H-2 restriction of contact inhibition of epithelial cells. Nature. 1979 Sep 20;281(5728):222–223. doi: 10.1038/281222a0. [DOI] [PubMed] [Google Scholar]
  10. De Giovanni C., Palmieri G., Nicoletti G., Landuzzi L., Scotlandi K., Bontadini A., Tazzari P. L., Sensi M., Santoni A., Nanni P. Immunological and non-immunological influence of H-2Kb gene transfection on the metastatic ability of B16 melanoma cells. Int J Cancer. 1991 May 10;48(2):270–276. doi: 10.1002/ijc.2910480220. [DOI] [PubMed] [Google Scholar]
  11. Dejana E., Bertocchi F., Bortolami M. C., Regonesi A., Tonta A., Breviario F., Giavazzi R. Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. J Clin Invest. 1988 Oct;82(4):1466–1470. doi: 10.1172/JCI113753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dejana E., Colella S., Languino L. R., Balconi G., Corbascio G. C., Marchisio P. C. Fibrinogen induces adhesion, spreading, and microfilament organization of human endothelial cells in vitro. J Cell Biol. 1987 May;104(5):1403–1411. doi: 10.1083/jcb.104.5.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dejana E., Lampugnani M. G., Giorgi M., Gaboli M., Federici A. B., Ruggeri Z. M., Marchisio P. C. Von Willebrand factor promotes endothelial cell adhesion via an Arg-Gly-Asp-dependent mechanism. J Cell Biol. 1989 Jul;109(1):367–375. doi: 10.1083/jcb.109.1.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Doherty P. C., Knowles B. B., Wettstein P. J. Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function. Adv Cancer Res. 1984;42:1–65. doi: 10.1016/s0065-230x(08)60455-8. [DOI] [PubMed] [Google Scholar]
  15. Elliott B. E., Carlow D. A., Rodricks A. M., Wade A. Perspectives on the role of MHC antigens in normal and malignant cell development. Adv Cancer Res. 1989;53:181–245. doi: 10.1016/s0065-230x(08)60282-1. [DOI] [PubMed] [Google Scholar]
  16. Gattoni-Celli S., Strauss R. M., Willett C. G., Pozzatti R., Isselbacher K. J. Modulation of the transformed and neoplastic phenotype of rat fibroblasts by MHC-I gene expression. Cancer Res. 1989 Jun 15;49(12):3392–3395. [PubMed] [Google Scholar]
  17. Giavazzi R., Garofalo A., Bani M. R., Abbate M., Ghezzi P., Boraschi D., Mantovani A., Dejana E. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res. 1990 Aug 1;50(15):4771–4775. [PubMed] [Google Scholar]
  18. Gopas J., Rager-Zisman B., Bar-Eli M., Hämmerling G. J., Segal S. The relationship between MHC antigen expression and metastasis. Adv Cancer Res. 1989;53:89–115. doi: 10.1016/s0065-230x(08)60280-8. [DOI] [PubMed] [Google Scholar]
  19. Gorelik E., Jay G., Kim M., Hearing V. J., DeLeo A., McCoy J. P., Jr Effects of H-2Kb gene on expression of melanoma-associated antigen and lectin-binding sites on BL6 melanoma cells. Cancer Res. 1991 Oct 1;51(19):5212–5218. [PubMed] [Google Scholar]
  20. Graf L. H., Jr, Kaplan P., Silagi S. Efficient DNA-mediated transfer of selectable genes and unselected sequences into differentiated and undifferentiated mouse melanoma clones. Somat Cell Mol Genet. 1984 Mar;10(2):139–151. doi: 10.1007/BF01534903. [DOI] [PubMed] [Google Scholar]
  21. Haliotis T., Carlow D. A., Elliott B. E. Nonimmunological aspects of MHC function in the regulation of cell proliferation and the malignant phenotype. Cancer Cells. 1990 Mar;2(3):86–90. [PubMed] [Google Scholar]
  22. Honda H., Rostami A. Expression of major histocompatibility complex class I antigens in rat muscle cultures: the possible developmental role in myogenesis. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7007–7011. doi: 10.1073/pnas.86.18.7007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Humphries M. J., Yamada K. M., Olden K. Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells. J Clin Invest. 1988 Mar;81(3):782–790. doi: 10.1172/JCI113384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hynes R. O. Integrins: a family of cell surface receptors. Cell. 1987 Feb 27;48(4):549–554. doi: 10.1016/0092-8674(87)90233-9. [DOI] [PubMed] [Google Scholar]
  25. Kojima N., Shiota M., Sadahira Y., Handa K., Hakomori S. Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells. J Biol Chem. 1992 Aug 25;267(24):17264–17270. [PubMed] [Google Scholar]
  26. Korach S., Poupon M. F., Du Villard J. A., Becker M. Differential adhesiveness of rhabdomyosarcoma-derived cloned metastatic cell lines to vascular endothelial monolayers. Cancer Res. 1986 Jul;46(7):3624–3629. [PubMed] [Google Scholar]
  27. Lampugnani M. G., Resnati M., Dejana E., Marchisio P. C. The role of integrins in the maintenance of endothelial monolayer integrity. J Cell Biol. 1991 Feb;112(3):479–490. doi: 10.1083/jcb.112.3.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lauri D., Bertomeu M. C., Orr F. W., Bastida E., Sauder D., Buchanan M. R. Interleukin-1 increases tumor cell adhesion to endothelial cells through an RGD dependent mechanism: in vitro and in vivo studies. Clin Exp Metastasis. 1990 Jan-Feb;8(1):27–32. doi: 10.1007/BF00155590. [DOI] [PubMed] [Google Scholar]
  29. Ljunggren H. G., Kärre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990 Jul;11(7):237–244. doi: 10.1016/0167-5699(90)90097-s. [DOI] [PubMed] [Google Scholar]
  30. Martìn-Padura I., Mortarini R., Lauri D., Bernasconi S., Sanchez-Madrid F., Parmiani G., Mantovani A., Anichini A., Dejana E. Heterogeneity in human melanoma cell adhesion to cytokine activated endothelial cells correlates with VLA-4 expression. Cancer Res. 1991 Apr 15;51(8):2239–2241. [PubMed] [Google Scholar]
  31. McCarthy J. B., Basara M. L., Palm S. L., Sas D. F., Furcht L. T. The role of cell adhesion proteins--laminin and fibronectin--in the movement of malignant and metastatic cells. Cancer Metastasis Rev. 1985;4(2):125–152. doi: 10.1007/BF00050692. [DOI] [PubMed] [Google Scholar]
  32. Nicolson G. L. Metastatic tumor cell attachment and invasion assay utilizing vascular endothelial cell monolayers. J Histochem Cytochem. 1982 Mar;30(3):214–220. doi: 10.1177/30.3.7061823. [DOI] [PubMed] [Google Scholar]
  33. Nicolson G. L. Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev. 1988 Jun;7(2):143–188. doi: 10.1007/BF00046483. [DOI] [PubMed] [Google Scholar]
  34. Rice G. E., Bevilacqua M. P. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science. 1989 Dec 8;246(4935):1303–1306. doi: 10.1126/science.2588007. [DOI] [PubMed] [Google Scholar]
  35. Rice G. E., Gimbrone M. A., Jr, Bevilacqua M. P. Tumor cell-endothelial interactions. Increased adhesion of human melanoma cells to activated vascular endothelium. Am J Pathol. 1988 Nov;133(2):204–210. [PMC free article] [PubMed] [Google Scholar]
  36. Rice G. E., Munro J. M., Bevilacqua M. P. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med. 1990 Apr 1;171(4):1369–1374. doi: 10.1084/jem.171.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ruoslahti E., Giancotti F. G. Integrins and tumor cell dissemination. Cancer Cells. 1989 Dec;1(4):119–126. [PubMed] [Google Scholar]
  38. Saiki I., Iida J., Murata J., Ogawa R., Nishi N., Sugimura K., Tokura S., Azuma I. Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules. Cancer Res. 1989 Jul 15;49(14):3815–3822. [PubMed] [Google Scholar]
  39. Schirrmacher V., Cheingsong-Popov R., Arnheiter H. Hepatocyte-tumor cell interaction in vitro. I. Conditions for rosette formation and inhibition by anti-H-2 antibody. J Exp Med. 1980 Apr 1;151(4):984–989. doi: 10.1084/jem.151.4.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sunday M. E., Isselbacher K. J., Gattoni-Celli S., Willett C. G. Altered growth of a human neuroendocrine carcinoma line after transfection of a major histocompatibility complex class I gene. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4700–4704. doi: 10.1073/pnas.86.12.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tanaka K., Yoshioka T., Bieberich C., Jay G. Role of the major histocompatibility complex class I antigens in tumor growth and metastasis. Annu Rev Immunol. 1988;6:359–380. doi: 10.1146/annurev.iy.06.040188.002043. [DOI] [PubMed] [Google Scholar]
  42. Varani J., Grimstad I. A., Knibbs R. N., Hovig T., McCoy J. P. Attachment, spreading and growth in vitro of highly malignant and low malignant murine fibrosarcoma cells. Clin Exp Metastasis. 1985 Jan-Mar;3(1):45–59. doi: 10.1007/BF01758953. [DOI] [PubMed] [Google Scholar]
  43. Wallich R., Bulbuc N., Hämmerling G. J., Katzav S., Segal S., Feldman M. Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature. 1985 May 23;315(6017):301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]
  44. Wellicome S. M., Thornhill M. H., Pitzalis C., Thomas D. S., Lanchbury J. S., Panayi G. S., Haskard D. O. A monoclonal antibody that detects a novel antigen on endothelial cells that is induced by tumor necrosis factor, IL-1, or lipopolysaccharide. J Immunol. 1990 Apr 1;144(7):2558–2565. [PubMed] [Google Scholar]
  45. Wexler H. Accurate identification of experimental pulmonary metastases. J Natl Cancer Inst. 1966 Apr;36(4):641–645. doi: 10.1093/jnci/36.4.641. [DOI] [PubMed] [Google Scholar]
  46. Williams R. L., Courtneidge S. A., Wagner E. F. Embryonic lethalities and endothelial tumors in chimeric mice expressing polyoma virus middle T oncogene. Cell. 1988 Jan 15;52(1):121–131. doi: 10.1016/0092-8674(88)90536-3. [DOI] [PubMed] [Google Scholar]
  47. Williams R. L., Risau W., Zerwes H. G., Drexler H., Aguzzi A., Wagner E. F. Endothelioma cells expressing the polyoma middle T oncogene induce hemangiomas by host cell recruitment. Cell. 1989 Jun 16;57(6):1053–1063. doi: 10.1016/0092-8674(89)90343-7. [DOI] [PubMed] [Google Scholar]
  48. Zhu D., Cheng C. F., Pauli B. U. Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis. J Clin Invest. 1992 Jun;89(6):1718–1724. doi: 10.1172/JCI115773. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES