Circulating level of hepatocyte growth factor as a useful tumor marker in patients with early‐stage gastric carcinoma

Tanaka, Kouji; Miki, Chikao; Wakuda, Reiko; Kobayashi, Minàko; Tonouchi, Hitoshi; Kusunoki, Masato

doi:10.1080/00365520410005973

Cited by 30 publications

(17 citation statements)

References 10 publications

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“…HGF in serum is an indicator of ovarian carcinoma in females with a pelvic mass, and with poor prognosis in advanced ovarian cancer. Similar results have been demonstrated in studies evaluating HGF in gastric carcinoma, colorectal cancer and hepatocellular carcinoma (17)(18)(19). However, there has been no study evaluating HGF in NPC.…”

Section: Discussionsupporting

confidence: 71%

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

et al. 2012

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Abstract. Hepatocyte growth factor (HGF) and its receptor c-Met are important in the development and homeostasis of a variety of human malignancies. However, the role of the HGF/c-Met signaling pathway in nasopharyngeal carcinoma (NPC) has not been clearly elucidated. This study examined the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. RT-PCR was used to detect the HGF gene in CNE-1, CNE-2, HK-1, HONE-1 and SUNE-1 NPC cells. However, HGF gene expression was not detected in any of these cells. Using immunoblotting analysis, the Met25 protein was identified in HONE-1, HK-1 and CNE-1 cells. Results from fluorescence-activated cell sorting (FACS) analysis revealed that anti-Met25 mAb specifically bound Met-expressing HONE-1, HK-1 and CNE-1 cells. It was further demonstrated that exogenous HGF was able to stimulate the proliferation of HONE-1 and HK-1 cells and the healing of scrape wounds in HONE-1 NPC cells. Our results reveal the potential therapeutic applications of combination therapy with antibodies targeting HGF in NPC patients. IntroductionNasopharyngeal carcinoma (NPC) is one of the most common types of cancer in South East Asia, and remains a cause of high morbidity in Southern China (1). In addition to its ability for rapid growth, NPC has a tendency to invade the adjacent regions and metastasize to the regional lymph nodes and distant organs. Despite the sequela of radiation, radiotherapy remains the standard treatment for NPC (2,3). However, only early stage NPC cases are able to obtain effective results, including good prognosis and function. The combination of radiotherapy and chemotherapy is crucial in the therapy of locoregional advanced cases of NPC (4). Although over 95% of biopsies belong to the WHO type Ⅱ or Ⅲ classification, which are sensitive to radiotherapy and chemotherapy, there are many treatment-failure cases (5). Thus, there is a requirement for new therapeutic targets and a better understanding of the mechanisms involved in the metastasis of NPC.The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are overexpressed and/or activated in a variety of human malignancies. The hepatocyte growth factor/ scatter factor (HGF/SF) and its receptor Met are important in the development, homeostasis, tumorigenesis, angiogenesis, invasion and metastasis of human malignancies (6). However, the mechanisms of the HGF/c-Met signaling pathway that contribute to the invasiveness of malignancies remain unknown. The Met receptor is frequently overexpressed in NPC patients, and high expression is associated with short patient survival (7). The availability of the Met receptor has been shown to modify NPC cell response to HGF. This finding enhanced our understanding of the mechanisms of signaling transduction in the HGF-induced progression of NPC. However, the role of the HGF/c-Met signaling pathway in NPC has not been clearly elucidated. In this study, we detected the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. Our r...

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Section: Discussionsupporting

confidence: 71%

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

et al. 2012

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“…It also has an indirect lymphangiogenic effect through the VEGFR-3 receptor [27] . HGF expression has previously been reported in several human cancers, and in some tumors its expression correlates with lymph node metastasis [12,19,[30][31][32][33] . PDGF expression is also found in several human cancers, including OSCCa [18,34,35] .…”

Section: Discussionmentioning

confidence: 99%

Lymphatic Microvessel Density and the Expression of Lymphangiogenic Factors in Oral Squamous Cell Carcinoma

Ali¹

2008

Med Princ Pract

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Objective: In this study, the expression of several lymphangiogenic growth factors was investigated to determine the mechanism underlying lymphangiogenesis in oral squamous cell carcinoma (OSCCa). Materials and Methods: An immunohistochemical study was performed to determine the lymphatic microvessel density (LMVD) and the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGF-I/II), and hepatocyte growth factor (HGF) in 25 OSCCa and 20 normal oral mucosal tissue samples. Results: Significantly higher levels of expression of VEGF, PDGF, bFGF, HGF, IGF-I, and IGF-II existed in OSCCa tissue compared to normal oral mucosal tissue (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.01, respectively; Mann-Whitney test). In OSCCa samples, significant positive correlations, based on the Spearman correlation test, existed between the LMVD and VEGF (r = 0.573; p < 0.01), PDGF (r = 0.559; p < 0.01), bFGF (r = 0.516; p < 0.01), HGF (r = 0.448; p < 0.05), and IGF-I (r = 0.6; p < 0.01), but no correlation existed between LMVD and IGF-II (r = 0.380; p > 0.05). Conclusion: These findings indicate that several growth factors may promote lymphangiogenesis in OSCCa. Future treatment for OSCCa utilizing antilymphangiogenic agents should target these different growth factor signaling pathways that are involved in lymphangiogenesis in OSCCa.

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“…Meanwhile, a high serum HGF concentration has been associated with a poor prognosis in many malignant neoplastic diseases, including colorectal, esophageal, gastric, and prostate cancer, as well as malignant myeloma (23)(24)(25). Where cancer treatment is concerned, high peripheral and portal HGF serum levels are related to a poor prognosis after hepatic resection in hepatocellular carcinoma (HCC) patients (26).…”

Section: Discussionmentioning

confidence: 99%

Impact of Serum Hepatocyte Growth Factor on Treatment Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non–Small Cell Lung Adenocarcinoma

Kondo

Arao

Sakai

et al. 2010

Clinical Cancer Research

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Purpose: The epidermal growth factor receptor (EGFR) mutation status has emerged as a validated biomarker for predicting the response to treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI) in patients with non-small cell lung cancer. However, the responses to EGFR-TKIs vary even among patients with EGFR mutations. We studied several other independently active biomarkers for EGFR-TKI treatment.Experimental Design: We retrospectively analyzed the serum concentrations of 13 molecules in a cohort of 95 patients with non-small cell lung adenocarcinoma who received EGFR-TKI treatment at three centers. The pretreatment serum concentrations of amphiregulin, β-cellulin, EGF, EGFR, epiregulin, fibroblast growth factor-basic, heparin-binding EGF-like growth factor, hepatocyte growth factor (HGF), platelet-derived growth factor β polypeptide, placental growth factor, tenascin C, transforming growth factor-α, and vascular endothelial growth factor (VEGF) were measured using enzyme-linked immunosorbent assay and a multiplex immunoassay system. The associations between clinical outcomes and these molecules were evaluated.Results: The concentrations of HGF and VEGF were significantly higher among patients with progressive disease than among those without progressive disease (P < 0.0001). HGF and VEGF were strongly associated with progression-free survival (PFS) and overall survival (OS) in a univariate Cox analysis (all tests for hazard ratio showed P < 0.0001). A stratified multivariate Cox model according to EGFR mutation status (mutant, n = 20; wild-type, n = 23; unknown, n = 52) showed that higher HGF levels were significantly associated with a shorter PFS and OS (P < 0.0001 for both PFS and OS). These observations were also consistent in the subset analyses.Conclusions: Serum HGF was strongly related to the outcome of EGFR-TKI treatment. Our results suggest that the serum HGF level could be used to refine the selection of patients expected to respond to EGFR-TKI treatment, warranting further prospective study. Clin Cancer Res; 16(18); 4616-24. ©2010 AACR.Selective epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) block signal transduction pathways implicated in the proliferation and survival of cancer cells (1-3), and show clinical activity against non-small cell lung carcinoma (NSCLC,. To date, four populations are known to have a better response to EGFR-TKIs: females, never-smokers, adenocarcinoma histology, and patients of East Asian ethnicity (4-6). Active EGFR mutation apparently confers a hyperresponsiveness to gefitinib among NSCLC patients (7,8). Such mutations affect the ATP-binding cleft of EGFR, and EGFR mutants exhibit constitutive tyrosine kinase activity. Most reported EGFR mutations are either point mutations in exons 18 (G719A/C) and 21 (L858R and L861Q) or in-frame deletions in exon 19 that eliminate five amino acids (ELREA) located at position 745 (9).A large-scale randomized study, the IRESSA Pan-Asia study (IPASS), comparing gefitinib monotherapy with carboplatin/pacli...

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Circulating level of hepatocyte growth factor as a useful tumor marker in patients with early‐stage gastric carcinoma

Cited by 30 publications

References 10 publications

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

Lymphatic Microvessel Density and the Expression of Lymphangiogenic Factors in Oral Squamous Cell Carcinoma

Impact of Serum Hepatocyte Growth Factor on Treatment Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non–Small Cell Lung Adenocarcinoma

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