ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Near-infrared fluorescence imaging with an MET-targeting probe for biopsy site selection in patients with oral potentially malignant disorders.Cell reports. Medicine · 2025Trial
- Met Receptor Tyrosine Kinase and Chemoprevention of Oral Cancer.Journal of the National Cancer Institute · 2018Trial
- Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.Investigational new drugs · 2013Trial
- Prognostic and predictive significance of plasma HGF and IL-8 in a phase III trial of chemoradiation with or without tirapazamine in locoregionally advanced head and neck cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Chorus line in oral squamous cell carcinoma: How stromal and immune players orchestrate tumor progression (Review).International journal of molecular medicine · 2026Review
- Cancer-associated fibroblasts in head and neck tumours: signalling networks and therapeutic implications with insights from vestibular schwannoma.Frontiers in cell and developmental biology · 2026Review
- Unraveling the impact of cancer-associated fibroblasts on lymphatic metastasis of head and neck squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Design and biological evaluation of peptide disruptors targeting YAP1-TEAD interaction for oral cancer.BMC oral health · 2025Article
- Leveraging liquid biopsy to uncover resistance mechanisms and guide personalized immunotherapy.Translational oncology · 2025Review
- Targeting HGF/c-MET signaling to regulate the tumor microenvironment: Implications for counteracting tumor immune evasion.Cell communication and signaling : CCS · 2025Review
- Evaluation of a Novel MET-Targeting Camelid-Derived Antibody in Head and Neck Cancer.Molecular pharmaceutics · 2024Article
- Future investigative directions for novel therapeutic targets in head and neck cancer.Expert review of anticancer therapy · 2024Review
- Crosstalk between CAFs and tumour cells in head and neck cancer.Cell death discovery · 2024Review
- MET exon 14 skipping mutation drives cancer progression and recurrence via activation of SMAD2 signalling.British journal of cancer · 2024Article
- Insights into the glioblastoma tumor microenvironment: current and emerging therapeutic approaches.Frontiers in pharmacology · 2024Review
- Nanomedicine in HNSCC therapy-a challenge to conventional therapy.Frontiers in pharmacology · 2024Review
- Oral squamous cell carcinomas: state of the field and emerging directions.International journal of oral science · 2023Review
- Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma: opportunities and challenges.Cell death discovery · 2023Review
- The tumor ecosystem in head and neck squamous cell carcinoma and advances in ecotherapy.Molecular cancer · 2023Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe determined hepatocyte growth factor (HGF) and c-Met expression and signaling in human head and neck squamous cell carcinoma (HNSCC) cells and primary tissues and tested the ability of c-Met tyrosine kinase inhibitors (TKI) to block HGF-induced biological signaling. EXPERIMENTAL
designExpression and signaling were determined using immunoblotting, ELISA, and immunohistochemistry. Biological end points included wound healing, cell proliferation, and invasion. c-Met TKIs were tested for their ability to block HGF-induced signaling and biological effects in vitro and in xenografts established in nude mice.
resultsc-Met was expressed and functional in HNSCC cells. HGF was secreted by HNSCC tumor-derived fibroblasts, but not by HNSCC cells. Activation of c-Met promoted phosphorylation of AKT and mitogen-activated protein kinase as well as release of the inflammatory cytokine interleukin-8. Cell growth and wound healing were also stimulated by HGF. c-Met TKIs blocked HGF-induced signaling, interleukin-8 release, and wound healing. Enhanced invasion of HNSCC cells induced by the presence of tumor-derived fibroblasts was completely blocked with a HGF-neutralizing antibody. PF-2341066, a c-Met TKI, caused a 50% inhibition of HNSCC tumor growth in vivo with decreased proliferation and increased apoptosis within the tumors. In HNSCC tumor tissues, both HGF and c-Met protein were increased compared with expression in normal mucosa.
conclusionsThese results show that HGF acts mainly as a paracrine factor in HNSCC cells, the HGF/c-Met pathway is frequently up-regulated and functional in HNSCC, and a clinically relevant c-Met TKI shows antitumor activity in vivo. Blocking the HGF/c-Met pathway may be clinically useful for the treatment of HNSCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.