Serum hepatocyte growth factor activator inhibitor type I (HAI‐I) and type 2 (HAI‐2) in prostate cancer

Nagakawa, Osamu; Yamagishi, Toshiya; Akashi, Takuya; Nagaike, Kazuhiro; Fuse, Hideki

doi:10.1002/pros.20301

Cited by 16 publications

(11 citation statements)

References 25 publications

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“…However, another study observed using immunohistochemistry indicated that HAI-1 expression levels were reduced in all grades of prostate cancer specimens (40). According to current research, HAI-1 may exhibit different functions in different types of cancer or even at different stages/sites in the same type of cancer (26,32,37,40,47). However, the differences in measuring HAI-1 expression levels, the lack of standardized methods (including antibody) among studies create difficulties in reaching a conclusion regarding HAI-1 expression in cancer and its association with clinicopathological parameters.…”

Section: Hai-1 Functional Domains and Proteases Inhibited By Hai-1mentioning

confidence: 59%

“…The mean serum levels of HAI-1 in 118 patients with prostate cancer were reported to be significantly higher than those in 27 patients with benign prostatic hyperplasia. Furthermore, increased HAI-1 levels in serum were associated with distant metastasis and the development of hormone-resistance in prostate cancer (47). However, another study observed using immunohistochemistry indicated that HAI-1 expression levels were reduced in all grades of prostate cancer specimens (40).…”

Section: Hai-1 Functional Domains and Proteases Inhibited By Hai-1mentioning

confidence: 96%

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Hepatocyte growth factor activator inhibitor type-1 in cancer: Advances and perspectives (Review)

Zheng¹,

Wu²,

Cao³

et al. 2014

Molecular Medicine Reports

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Abstract. Cancer is one of the most common diseases, with high morbidity and mortality rates. Large-scale efforts have been made to understand the pathogenesis of the disease, particularly in the advanced stages, in order to develop effective therapeutic approaches. Hepatocyte growth factor activator inhibitor type-1 (HAI-1), also known as serine protease inhibitor Kunitz type 1, inhibits the activity of several trypsin-like serine proteases. In particular, HAI-1 suppresses hepatocyte growth factor (HGF) activator and matriptase, resulting in subsequent inhibition of HGF/scatter factor and macrophage-stimulating protein (MSP). HGF and MSP are involved in cancer development and progression, via the receptors Met receptor tyrosine kinase (RTK) and Ron RTK, respectively. Therefore, HAI-1-mediated downregulation of HGF and MSP signaling may suppress tumorigenesis and progression in certain types of cancers. Abnormal HAI-1 expression levels have been observed in various types of human cancer. The exact function of HAI-1 in cancer pathogenesis, however, has not been fully elucidated. In this review, the focus is on the potential impact of aberrant HAI-1 expression levels on tumorigenesis and progression, the underlying mechanisms, and areas that require further investigation to clarify the precise role of HAI-1 in cancer.

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Section: Hai-1 Functional Domains and Proteases Inhibited By Hai-1mentioning

confidence: 59%

Section: Hai-1 Functional Domains and Proteases Inhibited By Hai-1mentioning

confidence: 96%

Hepatocyte growth factor activator inhibitor type-1 in cancer: Advances and perspectives (Review)

Zheng¹,

Wu²,

Cao³

et al. 2014

Molecular Medicine Reports

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“…HAI-1 may have a role in the progression of many cancers (Parr and Jiang, 2006) and has been suggested as a serum marker for prostate cancer (Nagakawa et al , 2006). Expression of HAI-1 is inversely related to invasion and metastasis (Parr and Jiang, 2001), and low expression is considered to be an indicator of poor prognosis in some cancers (Nakamura et al , 2009).…”

Section: Discussionmentioning

confidence: 99%

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

et al. 2013

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Background:Proteomic discovery of cancer biomarkers in body fluids is challenging because of their low abundance in a complex background. Altered gene expression in tumours may not reflect protein levels in body fluids. We have tested combining gene expression profiling of tumours with proteomic analysis of cancer cell line secretomes as a strategy to discover urinary biomarkers for bladder cancer.Methods:We used shotgun proteomics to identify proteins secreted by three bladder cancer cell lines. Secreted proteins with high mRNA levels in bladder tumours relative to normal urothelium were assayed by ELISA in urine samples from 642 patients.Results:Midkine and HAI-1 were significantly increased in bladder cancer patients, with the highest levels in invasive disease (area under the receiver operating characteristic curve 0.89 vs non-cancer). The urinary concentration of both proteins was too high to be explained by bladder cancer associated haematuria and most likely arises by direct tumour secretion.Conclusions:This ‘dual-omic' strategy identified tumour secreted proteins whose urine concentrations are increased significantly by bladder cancer. Combined secretome-transcriptome analysis may be more useful than direct proteomic analysis of body fluids for biomarker discovery in both bladder cancer and other tumour types.

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“…The elevation of HGFA and reduction of HAIs have been reported in a variety of tumors, indicating that the disruption of the balance between HGF activation and inhibition may favor tumor formation [29,30,31]. In addition, clinical data show that HAIs are inversely correlated with patient prognosis in different types of cancers, which further strengthens the potential role of HAIs as novel prognostic markers [32,33,34,35,36,37]. Recent research evidence suggested the therapeutic potential of recombinant HAI proteins for the treatment of a variety of cancers, including prostate, breast, and ovarian cancer [35,38,39].…”

Section: Mechanism Of Action: Targeting the Hgf Ligand Vs Targetimentioning

confidence: 77%

Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

2015

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The hepatocyte growth factor (HGF): MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.

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Serum hepatocyte growth factor activator inhibitor type I (HAI‐I) and type 2 (HAI‐2) in prostate cancer

Abstract: HAI-1 may be a potential tumor marker for prostate cancer. Further studies in large groups of patients are needed to define the clinical value of HAI-1.

Cited by 16 publications

References 25 publications

Hepatocyte growth factor activator inhibitor type-1 in cancer: Advances and perspectives (Review)

Hepatocyte growth factor activator inhibitor type-1 in cancer: Advances and perspectives (Review)

Combined proteome and transcriptome analyses for the discovery of urinary biomarkers for urothelial carcinoma

Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

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