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

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

F Bussolino, MF Di Renzo, M Ziche, E Bocchietto, M Olivero, L Naldini, G Gaudino, L Tamagnone, A Coffer and PM Comoglio
Department of Genetics, Biology and Medical Chemistry, University of Torino.

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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Giacobini, P., Giampietro, C., Fioretto, M., Maggi, R., Cariboni, A., Perroteau, I., Fasolo, A. (2002). Hepatocyte Growth Factor/Scatter Factor Facilitates Migration of GN-11 Immortalized LHRH Neurons. Endocrinology 143: 3306-3315 [Abstract] [Full Text]
LIU, F., SCHAPHORST, K. L., VERIN, A. D., JACOBS, K., BIRUKOVA, A., DAY, R. M., BOGATCHEVA, N., BOTTARO, D. P., GARCIA, J. G. N. (2002). Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3{beta}. FASEB J. 16: 950-962 [Abstract] [Full Text]
Purdie, K. J., Whitley, G. St.J., Johnstone, A. P., Cartwright, J. E. (2002). Hepatocyte growth factor-induced endothelial cell motility is mediated by the upregulation of inducible nitric oxide synthase expression. Cardiovasc Res 54: 659-668 [Abstract] [Full Text]
Yoshida, S., Harada, T., Iwabe, T., Taniguchi, F., Fujii, A., Sakamoto, Y., Yamauchi, N., Shiota, G., Terakawa, N. (2002). Induction of Hepatocyte Growth Factor in Stromal Cells by Tumor-Derived Basic Fibroblast Growth Factor Enhances Growth and Invasion of Endometrial Cancer. J. Clin. Endocrinol. Metab. 87: 2376-2383 [Abstract] [Full Text]
Grenier, A., Chollet-Martin, S., Crestani, B., Delarche, C., El Benna, J., Boutten, A., Andrieu, V., Durand, G., Gougerot-Pocidalo, M.-A., Aubier, M., Dehoux, M. (2002). Presence of a mobilizable intracellular pool of hepatocyte growth factor in human polymorphonuclear neutrophils. Blood 99: 2997-3004 [Abstract] [Full Text]
Muller, M., Morotti, A., Ponzetto, C. (2002). Activation of NF-{kappa}B Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis. Mol. Cell. Biol. 22: 1060-1072 [Abstract] [Full Text]
Cacciotti, P., Strizzi, L., Vianale, G., Iaccheri, L., Libener, R., Porta, C., Tognon, M., Gaudino, G., Mutti, L. (2002). The Presence of Simian-Virus 40 Sequences in Mesothelioma and Mesothelial Cells Is Associated with High Levels of Vascular Endothelial Growth Factor. Am. J. Respir. Cell Mol. Bio. 26: 189-193 [Abstract] [Full Text]
Rampino, T., Cancarini, G., Gregorini, M., Guallini, P., Maggio, M., Ranghino, A., Soccio, G., Dal Canton, A. (2001). Hepatocyte Growth Factor/Scatter Factor Released during Peritonitis Is Active on Mesothelial Cells. Am. J. Pathol. 159: 1275-1285 [Abstract] [Full Text]
Danilkovitch-Miagkova, A., Miagkov, A., Skeel, A., Nakaigawa, N., Zbar, B., Leonard, E. J. (2001). Oncogenic Mutants of RON and MET Receptor Tyrosine Kinases Cause Activation of the {beta}-Catenin Pathway. Mol. Cell. Biol. 21: 5857-5868 [Abstract] [Full Text]
Care, A., Felicetti, F., Meccia, E., Bottero, L., Parenza, M., Stoppacciaro, A., Peschle, C., Colombo, M. P. (2001). HOXB7: A Key Factor for Tumor-associated Angiogenic Switch. Cancer Res. 61: 6532-6539 [Abstract] [Full Text]
Medico, E., Gentile, A., Celso, C. L., Williams, T. A., Gambarotta, G., Trusolino, L., Comoglio, P. M. (2001). Osteopontin Is an Autocrine Mediator of Hepatocyte Growth Factor-induced Invasive Growth. Cancer Res. 61: 5861-5868 [Abstract] [Full Text]
Dong, G., Chen, Z., Li, Z.-Y., Yeh, N. T., Bancroft, C. C., Van Waes, C. (2001). Hepatocyte Growth Factor/Scatter Factor-induced Activation of MEK and PI3K Signal Pathways Contributes to Expression of Proangiogenic Cytokines Interleukin-8 and Vascular Endothelial Growth Factor in Head and Neck Squamous Cell Carcinoma. Cancer Res. 61: 5911-5918 [Abstract] [Full Text]
Jiang, W. G., Grimshaw, D., Lane, J., Martin, T. A., Abounder, R., Laterra, J., Mansel, R. E. (2001). A Hammerhead Ribozyme Suppresses Expression of Hepatocyte Growth Factor/Scatter Factor Receptor c-MET and Reduces Migration and Invasiveness of Breast Cancer Cells. Clin. Cancer Res. 7: 2555-2562 [Abstract] [Full Text]
Ueda, H., Nakamura, T., Matsumoto, K., Sawa, Y., Matsuda, H., Nakamura, T. (2001). A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats. Cardiovasc Res 51: 41-50 [Abstract] [Full Text]
Shaharabany, M., Abramovitch, R., Kushnir, T., Tsarfaty, G., Ravid-Megido, M., Horev, J., Ron, R., Itzchak, Y., Tsarfaty, I. (2001). In Vivo Molecular Imaging of Met Tyrosine Kinase Growth Factor Receptor Activity in Normal Organs and Breast Tumors. Cancer Res. 61: 4873-4878 [Abstract] [Full Text]
Yamamoto, K., Morishita, R., Hayashi, S.-i., Matsushita, H., Nakagami, H., Moriguchi, A., Matsumoto, K., Nakamura, T., Kaneda, Y., Ogihara, T. (2001). Contribution of Bcl-2, but Not Bcl-xL and Bax, to Antiapoptotic Actions of Hepatocyte Growth Factor in Hypoxia-Conditioned Human Endothelial Cells. Hypertension 37: 1341-1348 [Abstract] [Full Text]
Audero, E., Cascone, I., Zanon, I., Previtali, S. C., Piva, R., Schiffer, D., Bussolino, F. (2001). Expression of Angiopoietin-1 in Human Glioblastomas Regulates Tumor-Induced Angiogenesis : In Vivo and In Vitro Studies. Arterioscler. Thromb. Vasc. Bio. 21: 536-541 [Abstract] [Full Text]