Hepatocyte growth factor, its receptor, and their potential value in cancer therapies

Jiang, Wen Guo; Martin, Tracey Amanda; Parr, Christian; Davies, Gaynor; Matsumoto, Kunio; Nakamura, Toshikazu

doi:10.1016/j.critrevonc.2004.09.004

Cited by 230 publications

(176 citation statements)

References 263 publications

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“…First, the HGF molecule is homologous to plasminogen in that both have an amino-terminal loop, several kringle domains (plasminogen 5, HGF 4), and a serine protease domain (15), the latter of which is proteolytically inactive in HGF due to changes in active site amino acids. Both plasminogen and HGF are synthesized and released extracellularly as single-chain, inactive proteins that require proteolytic cleavage for activation at a homologous Arg-Val peptide bond.…”

Section: Discussionmentioning

confidence: 99%

“…HGF is a polypeptide growth factor that is produced by mesenchymal cells, and acts upon target tissues via the c-met receptor (15). HGF has particular importance in lung repair due to its ability to stimulate proliferation and migration of alveolar epithelial cells, which are required to resurface denuded alveolar surfaces (reviewed in Ref.…”

mentioning

confidence: 99%

“…Conversely, interventions designed to increase HGF reduce scarring (22)(23)(24). For HGF to have its effect on target cells, it must undergo several extracellular processing events (15,16). HGF is synthesized and secreted as a latent, single-chain protein.…”

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confidence: 99%

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Plasminogen-Mediated Activation and Release of Hepatocyte Growth Factor from Extracellular Matrix

Matsuoka

Sisson

Nishiuma

et al. 2006

Am J Respir Cell Mol Biol

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Interventions that enhance plasminogen activation within the lung consistently limit the fibrosis that follows alveolar injury. However, this protective effect cannot be attributed solely to accelerated clearance of fibrin that forms as a provisional matrix after lung injury. To explore other mechanisms, we considered interactions between the plasminogen activation system and hepatocyte growth factor (HGF). HGF is known to have antifibrotic activity, but to do so, it must be both released from its sites of sequestration within extracellular matrix (ECM) and activated by proteolytic cleavage. A recent study using bleomycin-exposed mice showed that manipulations of the plasminogen activation system influenced the amount of free HGF within bronchoalveolar lavage fluid without affecting total lung HGF mRNA or protein. To elucidate the mechanisms, we studied the role of plasminogen activation in fibroblastmediated HGF release and activation. We found that NIH3T3 and mouse lung fibroblasts release ECM-bound HGF in a plasminogendependent fashion. The plasminogen effect was lost when lung fibroblasts from urokinase-type plasminogen activator (uPA)-deficient mice were used, and was increased by fibroblasts from plasminogen activator inhibitor (PAI)-1-deficient mice. Plasminogen addition to NIH3T3 or mouse lung fibroblasts increased conversion of pro-HGF to its active form. The plasminogen effect on activation was lost when uPA-deficient fibroblasts were used and accentuated by PAI-1-deficient fibroblasts. In conjunction with the previous in vivo study, these results suggest that plasminogen activation can protect the lung against fibrosis by increasing the availability of active HGF.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Plasminogen-Mediated Activation and Release of Hepatocyte Growth Factor from Extracellular Matrix

Matsuoka

Sisson

Nishiuma

et al. 2006

Am J Respir Cell Mol Biol

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“…As mentioned above, targeting the EGF system has already become an established treatment modality in some types of tumours (Sridhar et al, 2003;Ranson, 2004), and has been shown to inhibit growth of NE GI tumour cells (Höpfner et al, 2003). Similarly, the pivotal role that HGF seems to play in cancer has led to the preclinical development of many types of targeting drugs, including antagonists, which compete with binding to the receptor, antibodies, which block the receptor, small-compound tyrosin kinase inhibitors, or other strategies that target downstream signals or secondary gene expression (Jiang et al, 2005).…”

Section: Ewsr1mentioning

confidence: 99%

“…Thus, new therapeutic options are needed. Targeting key growth-regulatory pathways is a promising approach in cancer treatment (Behe and Behr, 2002;Yee, 2002;Sridhar et al, 2003;Ranson, 2004;Jiang et al, 2005), and requires a thorough knowledge of molecular mechanisms involved in growth regulation of various tumour cell types.…”

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confidence: 99%

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

et al. 2005

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Targeting growth-regulatory pathways is a promising approach in cancer treatment. A prerequisite to the development of such therapies is characterisation of tumour growth regulation in the particular tumour cell type of interest. In order to gain insight into molecular mechanisms underlying proliferative responses in neuroendocrine (NE) gastrointestinal (GI) tumours, we investigated gene expression in human carcinoid BON cells after exposure to gastrin, hepatocyte growth factor (HGF), pituitary adenylate cyclaseactivating polypeptide or epidermal growth factor. We particularly focused on gastrin-and HGF-induced gene expression, and identified 95 gastrin-and 101 HGF-responsive genes. The majority of these genes are known mediators of processes central in tumour biology, and a number of them have been associated with poor prognosis and metastasis in cancer patients. Furthermore, we identified 12 genes that were regulated by all four factors, indicating that they may be universally regulated during NE GI tumour cell proliferation. Our findings provide useful hypotheses for further studies aimed to search for new therapeutic targets as well as tumour markers in NE GI tumours.

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c‐Met expression as an indicator of survival outcome in patients with oral tongue carcinoma

et al. 2010

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Background. Hepatocyte growth factor (HGF) can promote proliferation, invasion, and angiogenesis in various tumor cells. However, the prognosis according to expression of HGF/c-Met has not been reported in patients with squamous cell carcinoma of the oral tongue (SCCOT).Methods. Tumors from 61 patients with SCCOT were evaluated for the expression of HGF and c-Met by immunohistochemistry. For Western blot, we used fresh normal and cancer tissues from 3 patients with SCCOT.Results. The positive rates of HGF and c-Met immunostaining in SCCOT were 57.3% and 54.1%, respectively. The c-Met staining was significantly correlated with lymph node metastasis (p ¼ .005), tumor classification (p ¼ .004), and recurrence (p ¼ .018). Survival was significantly affected in patients with positive c-Met expression (p ¼ .003). HGF and c-Met were strongly expressed in cancer tissues on Western blot. Conclusion.The c-Met expression may play an important role in the progression and the survival outcome of patients with SCCOT.

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Hepatocyte growth factor, its receptor, and their potential value in cancer therapies

Cited by 230 publications

References 263 publications

Plasminogen-Mediated Activation and Release of Hepatocyte Growth Factor from Extracellular Matrix

Plasminogen-Mediated Activation and Release of Hepatocyte Growth Factor from Extracellular Matrix

Identification of novel growth factor-responsive genes in neuroendocrine gastrointestinal tumour cells

c‐Met expression as an indicator of survival outcome in patients with oral tongue carcinoma

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