Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells

Bone marrow (BM) stromal cells, which include macrophages, fibroblasts, endothelial cells, and adipocytes, have been shown to produce several factors that modulate the growth of BM progenitors. Hepatocyte growth factor (HGF) is a fibroblast-derived factor and has recently been shown to be a ligand for the c-met proto-oncogene, a member of the receptor class of tyrosine kinases. c-met messenger RNA (mRNA) is predominantly expressed in epithelial cells, but has been detected in several murine hematopoietic progenitor cell lines, suggesting that HGF and met might function during hematopoiesis. Here, BM cells were found to express both met mRNA and protein. Moreover, HGF was shown to synergize with interleukin-3 and granulocyte-macrophage colony-stimulating factor to stimulate colony formation of hematopoietic progenitor cells in vitro. These results show that, in addition to its activity on epithelial cells, HGF is a new member of the functionally related group of factors that modulate hematopoiesis.

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Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells

Blood ◽

10.1182/blood.v80.10.2454.2454 ◽

1992 ◽

Vol 80 (10) ◽

pp. 2454-2457 ◽

Cited By ~ 99

Author(s):

TE Kmiecik ◽

JR Keller ◽

E Rosen ◽

GF Vande Woude

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Hepatocyte Growth Factor ◽

Progenitor Cells ◽

Messenger Rna ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor Cell ◽

Hematopoietic Progenitor ◽

Hepatocyte Growth

Abstract Bone marrow (BM) stromal cells, which include macrophages, fibroblasts, endothelial cells, and adipocytes, have been shown to produce several factors that modulate the growth of BM progenitors. Hepatocyte growth factor (HGF) is a fibroblast-derived factor and has recently been shown to be a ligand for the c-met proto-oncogene, a member of the receptor class of tyrosine kinases. c-met messenger RNA (mRNA) is predominantly expressed in epithelial cells, but has been detected in several murine hematopoietic progenitor cell lines, suggesting that HGF and met might function during hematopoiesis. Here, BM cells were found to express both met mRNA and protein. Moreover, HGF was shown to synergize with interleukin-3 and granulocyte-macrophage colony-stimulating factor to stimulate colony formation of hematopoietic progenitor cells in vitro. These results show that, in addition to its activity on epithelial cells, HGF is a new member of the functionally related group of factors that modulate hematopoiesis.

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Differentiation of hematopoietic progenitor cells towards the myeloid and B-lymphoid lineage by hepatocyte growth factor (HGF) and thrombopoietin (TPO) together with early acting cytokines

European Journal Of Haematology ◽

10.1111/j.1600-0609.2006.00673.x ◽

2006 ◽

Vol 77 (2) ◽

pp. 134-144 ◽

Cited By ~ 5

Author(s):

Jochen Grassinger ◽

Gunnar Mueller ◽

Matthias Zaiss ◽

Leoni A. Kunz-Schughart ◽

Reinhard Andreesen ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Progenitor Cells ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Lymphoid Lineage ◽

B Lymphoid ◽

Hepatocyte Growth

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Hepatocyte growth factor mobilizes and recruits hematopoietic progenitor cells into liver through a stem cell factor-mediated mechanism

Hepatology Research ◽

10.1111/j.1872-034x.2010.00647.x ◽

2010 ◽

Vol 40 (7) ◽

pp. 711-719 ◽

Cited By ~ 13

Author(s):

Fumihito Tajima ◽

Hiroyuki Tsuchiya ◽

Kenichi Nishikawa ◽

Motoyuki Kataoka ◽

Ichiro Hisatome ◽

...

Keyword(s):

Stem Cell ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Progenitor Cells ◽

Stem Cell Factor ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Hepatocyte Growth

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Hepatocyte Growth Factor Stimulates Growth of Hematopoietic Progenitor Cells

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1993.1801 ◽

1993 ◽

Vol 194 (1) ◽

pp. 178-186 ◽

Cited By ~ 32

Author(s):

K. Mizuno ◽

O. Higuchi ◽

J.N. Ihle ◽

T. Nakamura

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Progenitor Cells ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Hepatocyte Growth

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Analysis of Progestin Effects on Hepatocyte Growth Factor Signaling Pathways in Relation to Proliferation and Alveolar Morphogenesis of Normal Mammary Epithelial Cells in Vitro

10.21236/ada416749 ◽

2003 ◽

Author(s):

Kyle T. Smith

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Hepatocyte Growth Factor ◽

Signaling Pathways ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Growth Factor Signaling ◽

Hepatocyte Growth ◽

Normal Mammary Epithelial

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Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia

Blood ◽

10.1182/blood.v70.4.1014.bloodjournal7041014 ◽

1987 ◽

Vol 70 (4) ◽

pp. 1014-1019 ◽

Cited By ~ 1

Author(s):

C Carlo-Stella ◽

M Cazzola ◽

A Gasner ◽

G Barosi ◽

L Dezza ◽

...

Keyword(s):

Progenitor Cells ◽

Progenitor Cell ◽

Hematopoietic Progenitor Cells ◽

Definitive Treatment ◽

Hematopoietic Progenitor Cell ◽

In Vitro Growth ◽

Hematopoietic Progenitor ◽

Myeloid Metaplasia ◽

Myelofibrosis With Myeloid Metaplasia

Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder due to clonal expansion of a pluripotent hematopoietic progenitor cell with secondary marrow fibrosis. No definitive treatment has as yet been devised for this condition, which shows a marked variability in clinical course. To evaluate whether excessive hematopoietic progenitor cell proliferation could be controlled by recombinant human interferon alpha (rIFN-alpha) and gamma (rIFN-gamma), we studied the effects of these agents on the in vitro growth of pluripotent and lineage-restricted circulating hematopoietic progenitor cells in 18 patients with MMM. A significant increase in the growth (mean +/- 1 SEM) per milliliter of peripheral blood of CFU-GEMM (594 +/- 253), CFU-Mk (1,033 +/- 410), BFU-E (4,799 +/- 2,020) and CFU- GM (5,438 +/- 2,505) was found in patients as compared with normal controls. Both rIFN-alpha and rIFN-gamma (10 to 10(4) U/mL) produced a significant dose-dependent suppression of CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM growth. Concentrations of rIFN-alpha and rIFN-gamma causing 50% inhibition of colony formation were 37 and 163 U/mL for CFU-GEMM, 16 and 69 U/mL for CFU-Mk, 53 and 146 U/mL for BFU-E, and 36 and 187 U/mL for CFU-GM, respectively. A marked synergistic effect was found between rIFN-alpha and rIFN-gamma: combination of the two agents produced inhibitory effects greater than or equivalent to those of 10- to 100- fold higher concentrations of single agents. These studies (a) confirm that circulating hematopoietic progenitors are markedly increased in MMM, (b) indicate that these presumably abnormal progenitors are normally responsive to rIFNs in vitro, and (c) show that IFNs act in a synergistic manner when used in combination. Because rIFN-gamma can downregulate collagen synthesis in vivo, this lymphokine could be particularly useful in the treatment of patients with MMM.

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Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development.

The Journal of Cell Biology ◽

10.1083/jcb.123.1.223 ◽

1993 ◽

Vol 123 (1) ◽

pp. 223-235 ◽

Cited By ~ 480

Author(s):

E Sonnenberg ◽

D Meyer ◽

K M Weidner ◽

C Birchmeier

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Hepatocyte Growth Factor ◽

Tyrosine Kinase ◽

Cell Surface Receptor ◽

Mouse Development ◽

Scatter Factor ◽

Rnase Protection ◽

Hepatocyte Growth

Scatter factor/hepatocyte growth factor (SF/HGF) has potent motogenic, mitogenic, and morphogenetic activities on epithelial cells in vitro. The cell surface receptor for this factor was recently identified: it is the product of the c-met protooncogene, a receptor-type tyrosine kinase. We report here the novel and distinct expression patterns of SF/HGF and its receptor during mouse development, which was determined by a combination of in situ hybridization and RNase protection experiments. Predominantly, we detect transcripts of c-met in epithelial cells of various developing organs, whereas the ligand is expressed in distinct mesenchymal cells in close vicinity. In addition, transient SF/HGF and c-met expression is found at certain sites of muscle formation; transient expression of the c-met gene is also detected in developing motoneurons. SF/HGF and the c-met receptor might thus play multiple developmental roles, most notably, mediate a signal given by mesenchyme and received by epithelial. Mesenchymal signals are known to govern differentiation and morphogenesis of many epithelia, but the molecular nature of the signals has remained poorly understood. Therefore, the known biological activities of SF/HGF in vitro and the embryonal expression pattern reported here indicate that this mesenchymal factor can transmit morphogenetic signals in epithelial development and suggest a molecular mechanism for mesenchymal epithelial interactions.

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Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia

Blood ◽

10.1182/blood.v70.4.1014.1014 ◽

1987 ◽

Vol 70 (4) ◽

pp. 1014-1019 ◽

Cited By ~ 65

Author(s):

C Carlo-Stella ◽

M Cazzola ◽

A Gasner ◽

G Barosi ◽

L Dezza ◽

...

Keyword(s):

Progenitor Cells ◽

Progenitor Cell ◽

Hematopoietic Progenitor Cells ◽

Definitive Treatment ◽

Hematopoietic Progenitor Cell ◽

In Vitro Growth ◽

Hematopoietic Progenitor ◽

Myeloid Metaplasia ◽

Myelofibrosis With Myeloid Metaplasia

Abstract Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder due to clonal expansion of a pluripotent hematopoietic progenitor cell with secondary marrow fibrosis. No definitive treatment has as yet been devised for this condition, which shows a marked variability in clinical course. To evaluate whether excessive hematopoietic progenitor cell proliferation could be controlled by recombinant human interferon alpha (rIFN-alpha) and gamma (rIFN-gamma), we studied the effects of these agents on the in vitro growth of pluripotent and lineage-restricted circulating hematopoietic progenitor cells in 18 patients with MMM. A significant increase in the growth (mean +/- 1 SEM) per milliliter of peripheral blood of CFU-GEMM (594 +/- 253), CFU-Mk (1,033 +/- 410), BFU-E (4,799 +/- 2,020) and CFU- GM (5,438 +/- 2,505) was found in patients as compared with normal controls. Both rIFN-alpha and rIFN-gamma (10 to 10(4) U/mL) produced a significant dose-dependent suppression of CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM growth. Concentrations of rIFN-alpha and rIFN-gamma causing 50% inhibition of colony formation were 37 and 163 U/mL for CFU-GEMM, 16 and 69 U/mL for CFU-Mk, 53 and 146 U/mL for BFU-E, and 36 and 187 U/mL for CFU-GM, respectively. A marked synergistic effect was found between rIFN-alpha and rIFN-gamma: combination of the two agents produced inhibitory effects greater than or equivalent to those of 10- to 100- fold higher concentrations of single agents. These studies (a) confirm that circulating hematopoietic progenitors are markedly increased in MMM, (b) indicate that these presumably abnormal progenitors are normally responsive to rIFNs in vitro, and (c) show that IFNs act in a synergistic manner when used in combination. Because rIFN-gamma can downregulate collagen synthesis in vivo, this lymphokine could be particularly useful in the treatment of patients with MMM.

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