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. 1992 Nov 1;119(3):629–641. doi: 10.1083/jcb.119.3.629

Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth

PMCID: PMC2289675  PMID: 1383237

Abstract

Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful mitogen or motility factor in different cells, acting through the tyrosine kinase receptor encoded by the MET protooncogene. Endothelial cells express the MET gene and expose at the cell surface the mature protein (p190MET) made of a 50 kD (alpha) subunit disulfide linked to a 145-kD (beta) subunit. HGF binding to endothelial cells identifies two sites with different affinities. The higher affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. Sub- nanomolar concentrations of HGF, but not of a recombinant inactive precursor, stimulate the receptor kinase activity, cell proliferation and motility. HGF induces repairs of a wound in endothelial cell monolayer. HGF stimulates the scatter of endothelial cells grown on three-dimensional collagen gels, inducing an elongated phenotype. In the rabbit cornea, highly purified HGF promotes neovascularization at sub-nanomolar concentrations. HGF lacks activities related to hemostasis-thrombosis, inflammation and endothelial cells accessory functions. These data show that HGF is an in vivo potent angiogenic factor and in vitro induces endothelial cells to proliferate and migrate.

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Selected References

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  1. Asami O., Ihara I., Shimidzu N., Shimizu S., Tomita Y., Ichihara A., Nakamura T. Purification and characterization of hepatocyte growth factor from injured liver of carbon tetrachloride-treated rats. J Biochem. 1991 Jan;109(1):8–13. [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Pober J. S., Majeau G. R., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med. 1984 Aug 1;160(2):618–623. doi: 10.1084/jem.160.2.618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  4. Bottaro D. P., Rubin J. S., Faletto D. L., Chan A. M., Kmiecik T. E., Vande Woude G. F., Aaronson S. A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991 Feb 15;251(4995):802–804. doi: 10.1126/science.1846706. [DOI] [PubMed] [Google Scholar]
  5. Bussolino F., Camussi G., Baglioni C. Synthesis and release of platelet-activating factor by human vascular endothelial cells treated with tumor necrosis factor or interleukin 1 alpha. J Biol Chem. 1988 Aug 25;263(24):11856–11861. [PubMed] [Google Scholar]
  6. Bussolino F., De Rossi M., Sica A., Colotta F., Wang J. M., Bocchietto E., Padura I. M., Bosia A., DeJana E., Mantovani A. Murine endothelioma cell lines transformed by polyoma middle T oncogene as target for and producers of cytokines. J Immunol. 1991 Oct 1;147(7):2122–2129. [PubMed] [Google Scholar]
  7. Bussolino F., Wang J. M., Defilippi P., Turrini F., Sanavio F., Edgell C. J., Aglietta M., Arese P., Mantovani A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 1989 Feb 2;337(6206):471–473. doi: 10.1038/337471a0. [DOI] [PubMed] [Google Scholar]
  8. Bussolino F., Ziche M., Wang J. M., Alessi D., Morbidelli L., Cremona O., Bosia A., Marchisio P. C., Mantovani A. In vitro and in vivo activation of endothelial cells by colony-stimulating factors. J Clin Invest. 1991 Mar;87(3):986–995. doi: 10.1172/JCI115107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  10. Chan A. M., King H. W., Deakin E. A., Tempest P. R., Hilkens J., Kroezen V., Edwards D. R., Wills A. J., Brookes P., Cooper C. S. Characterization of the mouse met proto-oncogene. Oncogene. 1988 Jun;2(6):593–599. [PubMed] [Google Scholar]
  11. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  12. Coffer A., Fellows J., Young S., Pappin D., Rahman D. Purification and characterization of biologically active scatter factor from ras-transformed NIH 3T3 conditioned medium. Biochem J. 1991 Aug 15;278(Pt 1):35–41. doi: 10.1042/bj2780035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Comoglio P. M., Di Renzo M. F., Tarone G., Giancotti F. G., Naldini L., Marchisio P. C. Detection of phosphotyrosine-containing proteins in the detergent-insoluble fraction of RSV-transformed fibroblasts by azobenzene phosphonate antibodies. EMBO J. 1984 Mar;3(3):483–489. doi: 10.1002/j.1460-2075.1984.tb01834.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dejana E., Languino L. R., Polentarutti N., Balconi G., Ryckewaert J. J., Larrieu M. J., Donati M. B., Mantovani A., Marguerie G. Interaction between fibrinogen and cultured endothelial cells. Induction of migration and specific binding. J Clin Invest. 1985 Jan;75(1):11–18. doi: 10.1172/JCI111661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Di Renzo M. F., Narsimhan R. P., Olivero M., Bretti S., Giordano S., Medico E., Gaglia P., Zara P., Comoglio P. M. Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene. 1991 Nov;6(11):1997–2003. [PubMed] [Google Scholar]
  16. Ferracini R., Longati P., Naldini L., Vigna E., Comoglio P. M. Identification of the major autophosphorylation site of the Met/hepatocyte growth factor receptor tyrosine kinase. J Biol Chem. 1991 Oct 15;266(29):19558–19564. [PubMed] [Google Scholar]
  17. Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
  18. Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Furlong R. A., Takehara T., Taylor W. G., Nakamura T., Rubin J. S. Comparison of biological and immunochemical properties indicates that scatter factor and hepatocyte growth factor are indistinguishable. J Cell Sci. 1991 Sep;100(Pt 1):173–177. doi: 10.1242/jcs.100.1.173. [DOI] [PubMed] [Google Scholar]
  20. Gherardi E., Gray J., Stoker M., Perryman M., Furlong R. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5844–5848. doi: 10.1073/pnas.86.15.5844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gherardi E., Stoker M. Hepatocyte growth factor--scatter factor: mitogen, motogen, and met. Cancer Cells. 1991 Jun;3(6):227–232. [PubMed] [Google Scholar]
  22. Gherardi E., Stoker M. Hepatocytes and scatter factor. Nature. 1990 Jul 19;346(6281):228–228. doi: 10.1038/346228b0. [DOI] [PubMed] [Google Scholar]
  23. Giordano S., Di Renzo M. F., Ferracini R., Chiadò-Piat L., Comoglio P. M. p145, a protein with associated tyrosine kinase activity in a human gastric carcinoma cell line. Mol Cell Biol. 1988 Aug;8(8):3510–3517. doi: 10.1128/mcb.8.8.3510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Giordano S., Di Renzo M. F., Narsimhan R. P., Cooper C. S., Rosa C., Comoglio P. M. Biosynthesis of the protein encoded by the c-met proto-oncogene. Oncogene. 1989 Nov;4(11):1383–1388. [PubMed] [Google Scholar]
  25. Giordano S., Ponzetto C., Di Renzo M. F., Cooper C. S., Comoglio P. M. Tyrosine kinase receptor indistinguishable from the c-met protein. Nature. 1989 May 11;339(6220):155–156. doi: 10.1038/339155a0. [DOI] [PubMed] [Google Scholar]
  26. Gohda E., Tsubouchi H., Nakayama H., Hirono S., Sakiyama O., Takahashi K., Miyazaki H., Hashimoto S., Daikuhara Y. Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure. J Clin Invest. 1988 Feb;81(2):414–419. doi: 10.1172/JCI113334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gonzatti-Haces M., Seth A., Park M., Copeland T., Oroszlan S., Vande Woude G. F. Characterization of the TPR-MET oncogene p65 and the MET protooncogene p140 protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1988 Jan;85(1):21–25. doi: 10.1073/pnas.85.1.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Graziani A., Gramaglia D., Cantley L. C., Comoglio P. M. The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase. J Biol Chem. 1991 Nov 25;266(33):22087–22090. [PubMed] [Google Scholar]
  29. Higuchi O., Nakamura T. Identification and change in the receptor for hepatocyte growth factor in rat liver after partial hepatectomy or induced hepatitis. Biochem Biophys Res Commun. 1991 Apr 30;176(2):599–607. doi: 10.1016/s0006-291x(05)80226-8. [DOI] [PubMed] [Google Scholar]
  30. Ingber D. E., Folkman J. How does extracellular matrix control capillary morphogenesis? Cell. 1989 Sep 8;58(5):803–805. doi: 10.1016/0092-8674(89)90928-8. [DOI] [PubMed] [Google Scholar]
  31. Kan M., Zhang G. H., Zarnegar R., Michalopoulos G., Myoken Y., McKeehan W. L., Stevens J. I. Hepatocyte growth factor/hepatopoietin A stimulates the growth of rat kidney proximal tubule epithelial cells (RPTE), rat nonparenchymal liver cells, human melanoma cells, mouse keratinocytes and stimulates anchorage-independent growth of SV-40 transformed RPTE. Biochem Biophys Res Commun. 1991 Jan 15;174(1):331–337. doi: 10.1016/0006-291x(91)90524-b. [DOI] [PubMed] [Google Scholar]
  32. Kaufman R. J., Davies M. V., Pathak V. K., Hershey J. W. The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. Mol Cell Biol. 1989 Mar;9(3):946–958. doi: 10.1128/mcb.9.3.946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kueng W., Silber E., Eppenberger U. Quantification of cells cultured on 96-well plates. Anal Biochem. 1989 Oct;182(1):16–19. doi: 10.1016/0003-2697(89)90710-0. [DOI] [PubMed] [Google Scholar]
  34. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  35. Mantovani A., Bussolino F., Dejana E. Cytokine regulation of endothelial cell function. FASEB J. 1992 May;6(8):2591–2599. doi: 10.1096/fasebj.6.8.1592209. [DOI] [PubMed] [Google Scholar]
  36. Masumoto A., Yamamoto N. Sequestration of a hepatocyte growth factor in extracellular matrix in normal adult rat liver. Biochem Biophys Res Commun. 1991 Jan 15;174(1):90–95. doi: 10.1016/0006-291x(91)90489-t. [DOI] [PubMed] [Google Scholar]
  37. Matsumoto K., Hashimoto K., Yoshikawa K., Nakamura T. Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor. Exp Cell Res. 1991 Sep;196(1):114–120. doi: 10.1016/0014-4827(91)90462-4. [DOI] [PubMed] [Google Scholar]
  38. Michalopoulos G., Houck K. A., Dolan M. L., Leutteke N. C. Control of hepatocyte replication by two serum factors. Cancer Res. 1984 Oct;44(10):4414–4419. [PubMed] [Google Scholar]
  39. Miyazawa K., Tsubouchi H., Naka D., Takahashi K., Okigaki M., Arakaki N., Nakayama H., Hirono S., Sakiyama O., Takahashi K. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967–973. doi: 10.1016/0006-291x(89)92316-4. [DOI] [PubMed] [Google Scholar]
  40. Montesano R., Matsumoto K., Nakamura T., Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991 Nov 29;67(5):901–908. doi: 10.1016/0092-8674(91)90363-4. [DOI] [PubMed] [Google Scholar]
  41. Montesano R., Vassalli J. D., Baird A., Guillemin R., Orci L. Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7297–7301. doi: 10.1073/pnas.83.19.7297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Morimoto A., Okamura K., Hamanaka R., Sato Y., Shima N., Higashio K., Kuwano M. Hepatocyte growth factor modulates migration and proliferation of human microvascular endothelial cells in culture. Biochem Biophys Res Commun. 1991 Sep 16;179(2):1042–1049. doi: 10.1016/0006-291x(91)91924-2. [DOI] [PubMed] [Google Scholar]
  43. Nakamura T., Nawa K., Ichihara A., Kaise N., Nishino T. Purification and subunit structure of hepatocyte growth factor from rat platelets. FEBS Lett. 1987 Nov 30;224(2):311–316. doi: 10.1016/0014-5793(87)80475-1. [DOI] [PubMed] [Google Scholar]
  44. Nakamura T., Nawa K., Ichihara A. Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1450–1459. doi: 10.1016/0006-291x(84)91253-1. [DOI] [PubMed] [Google Scholar]
  45. Nakamura T., Nishizawa T., Hagiya M., Seki T., Shimonishi M., Sugimura A., Tashiro K., Shimizu S. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440–443. doi: 10.1038/342440a0. [DOI] [PubMed] [Google Scholar]
  46. Nakamura T., Teramoto H., Ichihara A. Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary cultures. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6489–6493. doi: 10.1073/pnas.83.17.6489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Naldini L., Vigna E., Ferracini R., Longati P., Gandino L., Prat M., Comoglio P. M. The tyrosine kinase encoded by the MET proto-oncogene is activated by autophosphorylation. Mol Cell Biol. 1991 Apr;11(4):1793–1803. doi: 10.1128/mcb.11.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Naldini L., Vigna E., Narsimhan R. P., Gaudino G., Zarnegar R., Michalopoulos G. K., Comoglio P. M. Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene. 1991 Apr;6(4):501–504. [PubMed] [Google Scholar]
  49. Naldini L., Weidner K. M., Vigna E., Gaudino G., Bardelli A., Ponzetto C., Narsimhan R. P., Hartmann G., Zarnegar R., Michalopoulos G. K. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 1991 Oct;10(10):2867–2878. doi: 10.1002/j.1460-2075.1991.tb07836.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Nawroth P. P., Handley D. A., Esmon C. T., Stern D. M. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci U S A. 1986 May;83(10):3460–3464. doi: 10.1073/pnas.83.10.3460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Osborn L. Leukocyte adhesion to endothelium in inflammation. Cell. 1990 Jul 13;62(1):3–6. doi: 10.1016/0092-8674(90)90230-c. [DOI] [PubMed] [Google Scholar]
  52. Park M., Dean M., Cooper C. S., Schmidt M., O'Brien S. J., Blair D. G., Vande Woude G. F. Mechanism of met oncogene activation. Cell. 1986 Jun 20;45(6):895–904. doi: 10.1016/0092-8674(86)90564-7. [DOI] [PubMed] [Google Scholar]
  53. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  54. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  55. Ponzetto C., Giordano S., Peverali F., Della Valle G., Abate M. L., Vaula G., Comoglio P. M. c-met is amplified but not mutated in a cell line with an activated met tyrosine kinase. Oncogene. 1991 Apr;6(4):553–559. [PubMed] [Google Scholar]
  56. Prat M., Narsimhan R. P., Crepaldi T., Nicotra M. R., Natali P. G., Comoglio P. M. The receptor encoded by the human c-MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors. Int J Cancer. 1991 Sep 30;49(3):323–328. doi: 10.1002/ijc.2910490302. [DOI] [PubMed] [Google Scholar]
  57. Rosen E. M., Meromsky L., Setter E., Vinter D. W., Goldberg I. D. Quantitation of cytokine-stimulated migration of endothelium and epithelium by a new assay using microcarrier beads. Exp Cell Res. 1990 Jan;186(1):22–31. doi: 10.1016/0014-4827(90)90205-o. [DOI] [PubMed] [Google Scholar]
  58. Rosen E. M., Meromsky L., Setter E., Vinter D. W., Goldberg I. D. Smooth muscle-derived factor stimulates mobility of human tumor cells. Invasion Metastasis. 1990;10(1):49–64. [PubMed] [Google Scholar]
  59. Rubin J. S., Chan A. M., Bottaro D. P., Burgess W. H., Taylor W. G., Cech A. C., Hirschfield D. W., Wong J., Miki T., Finch P. W. A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):415–419. doi: 10.1073/pnas.88.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Stoker M., Gherardi E., Perryman M., Gray J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature. 1987 May 21;327(6119):239–242. doi: 10.1038/327239a0. [DOI] [PubMed] [Google Scholar]
  62. Strain A. J., Ismail T., Tsubouchi H., Arakaki N., Hishida T., Kitamura N., Daikuhara Y., McMaster P. Native and recombinant human hepatocyte growth factors are highly potent promoters of DNA synthesis in both human and rat hepatocytes. J Clin Invest. 1991 May;87(5):1853–1857. doi: 10.1172/JCI115207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Tashiro K., Hagiya M., Nishizawa T., Seki T., Shimonishi M., Shimizu S., Nakamura T. Deduced primary structure of rat hepatocyte growth factor and expression of the mRNA in rat tissues. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3200–3204. doi: 10.1073/pnas.87.8.3200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Ullrich A., Schlessinger J. Signal transduction by receptors with tyrosine kinase activity. Cell. 1990 Apr 20;61(2):203–212. doi: 10.1016/0092-8674(90)90801-k. [DOI] [PubMed] [Google Scholar]
  65. Weidner K. M., Arakaki N., Hartmann G., Vandekerckhove J., Weingart S., Rieder H., Fonatsch C., Tsubouchi H., Hishida T., Daikuhara Y. Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001–7005. doi: 10.1073/pnas.88.16.7001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Weidner K. M., Behrens J., Vandekerckhove J., Birchmeier W. Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol. 1990 Nov;111(5 Pt 1):2097–2108. doi: 10.1083/jcb.111.5.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. 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]
  68. Zarnegar R., DeFrances M. C., Oliver L., Michalopoulos G. Identification and partial characterization of receptor binding sites for HGF on rat hepatocytes. Biochem Biophys Res Commun. 1990 Dec 31;173(3):1179–1185. doi: 10.1016/s0006-291x(05)80910-6. [DOI] [PubMed] [Google Scholar]
  69. Zarnegar R., Michalopoulos G. Purification and biological characterization of human hepatopoietin A, a polypeptide growth factor for hepatocytes. Cancer Res. 1989 Jun 15;49(12):3314–3320. [PubMed] [Google Scholar]
  70. Zarnegar R., Muga S., Rahija R., Michalopoulos G. Tissue distribution of hepatopoietin-A: a heparin-binding polypeptide growth factor for hepatocytes. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1252–1256. doi: 10.1073/pnas.87.3.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Ziche M., Alessandri G., Gullino P. M. Gangliosides promote the angiogenic response. Lab Invest. 1989 Dec;61(6):629–634. [PubMed] [Google Scholar]
  72. Zigmond S. H., Hirsch J. G. Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor. J Exp Med. 1973 Feb 1;137(2):387–410. doi: 10.1084/jem.137.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]

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