Hepatocyte growth factor stimulates extensive development of branching duct-like structures by cloned mammary gland epithelial cells

1995 ◽  
Vol 108 (2) ◽  
pp. 413-430 ◽  
Author(s):  
J.V. Soriano ◽  
M.S. Pepper ◽  
T. Nakamura ◽  
L. Orci ◽  
R. Montesano
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Conditioned Medium ◽  
Dependent Manner ◽  
Collagen Gels ◽  
Mammary Gland Epithelial Cells ◽  
Hepatocyte Growth

Although epithelial-mesenchymal (stromal) interactions are thought to play an important role in embryonic and postnatal development of the mammary gland, the underlying mechanisms are still poorly understood. To address this issue, we assessed the effect of fibroblast-derived diffusible factors on the growth and morphogenetic properties of a clonally derived subpopulation (clone TAC-2) of normal murine mammary gland (NMuMG) epithelial cells embedded in collagen gels. Under control conditions, TAC-2 mammary gland epithelial cells suspended within collagen gels formed either irregularly shaped cell aggregates or short branching cord-like structures. Addition of conditioned medium from Swiss 3T3 or MRC-5 fibroblasts dramatically stimulated cord formation by TAC-2 cells, resulting in the development of an extensive, highly arborized system of duct-like structures, which in appropriate sections were seen to contain a central lumen. The effect of fibroblast conditioned medium was completely abrogated by antibodies against hepatocyte growth factor (also known as scatter factor), a fibroblast-derived polypeptide that we have previously shown induces tubulogenesis by Madin-Darby canine kidney epithelial cells. Addition of exogenous recombinant human hepatocyte growth factor to collagen gel cultures of TAC-2 cells mimicked the tubulogenic activity of fibroblast conditioned medium by stimulating formation of branching duct-like structures in a dose-dependent manner, with a maximal 77-fold increase in cord length at 20 ng/ml. The effect of either fibroblast conditioned medium or hepatocyte growth factor was markedly potentiated by the simultaneous addition of hydrocortisone (1 microgram/ml), which also enhanced lumen formation. These results demonstrate that hepatocyte growth factor promotes the formation of branching duct-like structures by mammary gland epithelial cells in vitro, and suggest that it may act as a mediator of the inducing effect of mesenchyme (or stroma) on mammary gland development.

scholarly journals 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.

1993 ◽  
Vol 123 (1) ◽  
pp. 223-235 ◽  
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.

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

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2454-2457 ◽  
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.

Integrin-matrix interactions affect the form of the structures developing from human mammary epithelial cells in collagen or fibrin gels

1998 ◽  
Vol 111 (4) ◽  
pp. 521-532 ◽  
Author(s):  
D. Alford ◽  
D. Baeckstrom ◽  
M. Geyp ◽  
P. Pitha ◽  
J. Taylor-Papadimitriou
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Collagen Gels ◽  
Matrix Interaction ◽  
The Matrix ◽  
Mammary Morphogenesis ◽  
Hepatocyte Growth ◽  
Luminal Epithelial Cells ◽  
Cells Cultured

The HB2 cell line, developed from luminal epithelial cells cultured from milk, forms ball-like structures in collagen gels which show a uniform branching response to hepatocyte growth factor. The alpha2beta1 integrin is the major integrin expressed by luminal epithelial cells, and the role of this integrin in mammary morphogenesis has been analysed using HB2 cells cultured in collagen gels and antibodies which affect integrin function. Selectivity of response was followed by comparing effects on morphogenesis in fibrin, where the alphavbeta1 integrin interacts with the matrix. In the presence of hepatocyte growth factor, using alpha2 and beta1 antibodies in collagen and alphav and beta1 antibodies in fibrin, complete blocking of the cell-matrix interaction inhibits cell survival. With partial blocking of the integrin-ligand interaction, the cells proliferate but form dissociated colonies. Activating antibodies to the beta1 integrin subunit which enhance the matrix interaction dramatically inhibit the branching and motility responses to hepatocyte growth factor. A series of non-blocking alpha2 reactive antibodies also inhibit these responses specifically in or on collagen. Studies with ras-transfected HB2 cells emphasise the importance of the alpha2beta1 collagen interaction in the development of form since HB2ras cells, which express reduced levels of the alpha2beta1 integrin, form dissociated colonies in collagen but not in fibrin. Treatment of HB2ras cells with a beta1 activating antibody, however, induces the formation of compact colonies. Even though the ras-transformants form colonies in agar, complete blocking of the alpha2beta1/collagen interaction does not allow survival in collagen. The results indicate that in mammary morphogenesis, the strength of the interaction of integrins with the extracellular matrix modulates the response to motogenic factors and contributes to the definition of form.

Expression and action of hepatocyte growth factor in bovine endometrial stromal and epithelial cells in vitro

2001 ◽  
Vol 60 (4) ◽  
pp. 472-480 ◽  
Author(s):  
Shuko Murakami ◽  
Yoko Miyamoto ◽  
Chikako Fujiwara ◽  
Sakae Takeuchi ◽  
Sumio Takahashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Hepatocyte Growth

scholarly journals Hepatocyte Growth Factor Stimulates Proliferation, Migration, and Lumen Formation of Human Endometrial Epithelial Cells in Vitro

1997 ◽  
Vol 57 (4) ◽  
pp. 936-942 ◽  
Author(s):  
Junichi Sugawara ◽  
Takao Fukaya ◽  
Takashi Murakami ◽  
Hidemune Yoshida ◽  
Akira Yajima
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Hepatocyte Growth Factor ◽  
Lumen Formation ◽  
Hepatocyte Growth ◽  
Endometrial Epithelial Cells

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

1992 ◽  
Vol 119 (3) ◽  
pp. 629-641 ◽  
Author(s):  
F Bussolino ◽  
M F Di Renzo ◽  
M Ziche ◽  
E Bocchietto ◽  
M Olivero ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Monolayer ◽  
Angiogenic Factor ◽  
Tyrosine Kinase Receptor ◽  
Collagen Gels ◽  
Hepatocyte Growth

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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