Abstract
Hepatocyte growth factor (HGF) has been known as a multiple function factor, which also stimulates early haematopoiesis. In this study, we found that HGF was expressed at both the RNA and protein levels in acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). In patients with AML (n = 20) and CML (n = 5), bone marrow plasma HGF concentrations were 20.44 +/- 6.26 (mean +/- s.e.) ng ml-1 and 7.17 +/- 0.53 ng ml-1 respectively. These were significantly higher (P < 0.01) than the value for normal subjects (n = 26): mean 0.92 +/- 0.09 ng ml-1. Constitutive HGF production was observed in freshly prepared leukaemic blast cells from three patients with high HGF levels of bone marrow plasma. Expression of HGF mRNA was correlated with bone marrow plasma HGF levels. After complete remission was obtained in six patients, bone marrow plasma HGF levels were significantly decreased. In contrast, the HGF mRNA was less abundantly expressed in acute lymphoid leukaemia (ALL). In patients with ALL (n = 5), bone marrow plasma HGF concentration (0.69 +/- 0.14 ng ml-1) remained low within the value for normal subjects. These results suggest that some populations of myeloid lineage cells have the ability to produce HGF.
Full text
PDF![119](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03a/2074290/6a9e07fb8b9d/brjcancer00029-0123.png)
![120](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03a/2074290/d1f3b2096150/brjcancer00029-0124.png)
![121](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03a/2074290/2fb5b5f746cc/brjcancer00029-0125.png)
![122](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03a/2074290/5b90ebdbeeb1/brjcancer00029-0126.png)
![123](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03a/2074290/e03150abe017/brjcancer00029-0127.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Bussolino F., Di Renzo M. F., Ziche M., Bocchietto E., Olivero M., Naldini L., Gaudino G., Tamagnone L., Coffer A., Comoglio P. M. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol. 1992 Nov;119(3):629–641. doi: 10.1083/jcb.119.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Galimi F., Bagnara G. P., Bonsi L., Cottone E., Follenzi A., Simeone A., Comoglio P. M. Hepatocyte growth factor induces proliferation and differentiation of multipotent and erythroid hemopoietic progenitors. J Cell Biol. 1994 Dec;127(6 Pt 1):1743–1754. doi: 10.1083/jcb.127.6.1743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gherardi E., Stoker M. Hepatocyte growth factor--scatter factor: mitogen, motogen, and met. Cancer Cells. 1991 Jun;3(6):227–232. [PubMed] [Google Scholar]
- Giordano S., Zhen Z., Medico E., Gaudino G., Galimi F., Comoglio P. M. Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):649–653. doi: 10.1073/pnas.90.2.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gohda E., Tsubouchi H., Nakayama H., Hirono S., Takahashi K., Koura M., Hashimoto S., Daikuhara Y. Human hepatocyte growth factor in plasma from patients with fulminant hepatic failure. Exp Cell Res. 1986 Sep;166(1):139–150. doi: 10.1016/0014-4827(86)90514-8. [DOI] [PubMed] [Google Scholar]
- Grant D. S., Kleinman H. K., Goldberg I. D., Bhargava M. M., Nickoloff B. J., Kinsella J. L., Polverini P., Rosen E. M. Scatter factor induces blood vessel formation in vivo. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1937–1941. doi: 10.1073/pnas.90.5.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higashio K., Shima N., Goto M., Itagaki Y., Nagao M., Yasuda H., Morinaga T. Identity of a tumor cytotoxic factor from human fibroblasts and hepatocyte growth factor. Biochem Biophys Res Commun. 1990 Jul 16;170(1):397–404. doi: 10.1016/0006-291x(90)91287-3. [DOI] [PubMed] [Google Scholar]
- Hu Z., Evarts R. P., Fujio K., Marsden E. R., Thorgeirsson S. S. Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development in the rat. Am J Pathol. 1993 Jun;142(6):1823–1830. [PMC free article] [PubMed] [Google Scholar]
- Igawa T., Kanda S., Kanetake H., Saitoh Y., Ichihara A., Tomita Y., Nakamura T. Hepatocyte growth factor is a potent mitogen for cultured rabbit renal tubular epithelial cells. Biochem Biophys Res Commun. 1991 Jan 31;174(2):831–838. doi: 10.1016/0006-291x(91)91493-v. [DOI] [PubMed] [Google Scholar]
- Inaba M., Koyama H., Hino M., Okuno S., Terada M., Nishizawa Y., Nishino T., Morii H. Regulation of release of hepatocyte growth factor from human promyelocytic leukemia cells, HL-60, by 1,25-dihydroxyvitamin D3, 12-O-tetradecanoylphorbol 13-acetate, and dibutyryl cyclic adenosine monophosphate. Blood. 1993 Jul 1;82(1):53–59. [PubMed] [Google Scholar]
- Jücker M., Günther A., Gradl G., Fonatsch C., Krueger G., Diehl V., Tesch H. The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some cases of human leukemia and lymphoma. Leuk Res. 1994 Jan;18(1):7–16. doi: 10.1016/0145-2126(94)90003-5. [DOI] [PubMed] [Google Scholar]
- 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]
- Kinoshita T., Tashiro K., Nakamura T. Marked increase of HGF mRNA in non-parenchymal liver cells of rats treated with hepatotoxins. Biochem Biophys Res Commun. 1989 Dec 29;165(3):1229–1234. doi: 10.1016/0006-291x(89)92733-2. [DOI] [PubMed] [Google Scholar]
- Kmiecik T. E., Keller J. R., Rosen E., Vande Woude G. F. Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells. Blood. 1992 Nov 15;80(10):2454–2457. [PubMed] [Google Scholar]
- 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]
- Mizuno K., Higuchi O., Ihle J. N., Nakamura T. Hepatocyte growth factor stimulates growth of hematopoietic progenitor cells. Biochem Biophys Res Commun. 1993 Jul 15;194(1):178–186. doi: 10.1006/bbrc.1993.1801. [DOI] [PubMed] [Google Scholar]
- 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]
- Nagaike M., Hirao S., Tajima H., Noji S., Taniguchi S., Matsumoto K., Nakamura T. Renotropic functions of hepatocyte growth factor in renal regeneration after unilateral nephrectomy. J Biol Chem. 1991 Dec 5;266(34):22781–22784. [PubMed] [Google Scholar]
- Nakamura S., Gohda E., Matsunaga T., Yamamoto I., Minowada J. Production of hepatocyte growth factor by human haematopoietic cell lines. Cytokine. 1994 May;6(3):285–294. doi: 10.1016/1043-4666(94)90025-6. [DOI] [PubMed] [Google Scholar]
- Nakamura S., Gohda E., Matsuo Y., Yamamoto I., Minowada J. Significant amount of hepatocyte growth factor detected in blood and bone marrow plasma of leukaemia patients. Br J Haematol. 1994 Jul;87(3):640–642. doi: 10.1111/j.1365-2141.1994.tb08330.x. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- Nishino T., Hisha H., Nishino N., Adachi M., Ikehara S. Hepatocyte growth factor as a hematopoietic regulator. Blood. 1995 Jun 1;85(11):3093–3100. [PubMed] [Google Scholar]
- Nishino T., Kaise N., Sindo Y., Nishino N., Nishida T., Yasuda S., Masui Y. Promyelocytic leukemia cell line, HL-60, produces human hepatocyte growth factor. Biochem Biophys Res Commun. 1991 Nov 27;181(1):323–330. doi: 10.1016/s0006-291x(05)81421-4. [DOI] [PubMed] [Google Scholar]
- Noji S., Tashiro K., Koyama E., Nohno T., Ohyama K., Taniguchi S., Nakamura T. Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. Biochem Biophys Res Commun. 1990 Nov 30;173(1):42–47. doi: 10.1016/s0006-291x(05)81018-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Russell W. E., McGowan J. A., Bucher N. L. Partial characterization of a hepatocyte growth factor from rat platelets. J Cell Physiol. 1984 May;119(2):183–192. doi: 10.1002/jcp.1041190207. [DOI] [PubMed] [Google Scholar]
- Seki T., Ihara I., Sugimura A., Shimonishi M., Nishizawa T., Asami O., Hagiya M., Nakamura T., Shimizu S. Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte. Biochem Biophys Res Commun. 1990 Oct 15;172(1):321–327. doi: 10.1016/s0006-291x(05)80212-8. [DOI] [PubMed] [Google Scholar]
- Selden C., Jones M., Wade D., Hodgson H. Hepatotropin mRNA expression in human foetal liver development and in liver regeneration. FEBS Lett. 1990 Sep 17;270(1-2):81–84. doi: 10.1016/0014-5793(90)81239-k. [DOI] [PubMed] [Google Scholar]
- Tajima H., Matsumoto K., Nakamura T. Hepatocyte growth factor has potent anti-proliferative activity in various tumor cell lines. FEBS Lett. 1991 Oct 21;291(2):229–232. doi: 10.1016/0014-5793(91)81291-f. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Yanagita K., Matsumoto K., Sekiguchi K., Ishibashi H., Niho Y., Nakamura T. Hepatocyte growth factor may act as a pulmotrophic factor on lung regeneration after acute lung injury. J Biol Chem. 1993 Oct 5;268(28):21212–21217. [PubMed] [Google Scholar]
- Yanagita K., Nagaike M., Ishibashi H., Niho Y., Matsumoto K., Nakamura T. Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs. Biochem Biophys Res Commun. 1992 Jan 31;182(2):802–809. doi: 10.1016/0006-291x(92)91803-x. [DOI] [PubMed] [Google Scholar]
- Yukioka K., Inaba M., Furumitsu Y., Yukioka M., Nishino T., Goto H., Nishizawa Y., Morii H. Levels of hepatocyte growth factor in synovial fluid and serum of patients with rheumatoid arthritis and release of hepatocyte growth factor by rheumatoid synovial fluid cells. J Rheumatol. 1994 Dec;21(12):2184–2189. [PubMed] [Google Scholar]