Significance of heparanase in metastatic lymph nodes of cervical squamous cell cancer

Hu, Bin; Wang, Qing; Shi, Yingying; Lu, Shufang; Qu, Hongjie; Wang, Lu; Cui, Jinquan

doi:10.3892/ol.2017.5804

Cited by 3 publications

(1 citation statement)

References 30 publications

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“…Clinically, patients that were diagnosed as heparanase-positive exhibited a significantly higher rate of local and distant metastases as well as reduced postoperative survival, compared with patients that were diagnosed as heparanase-negative. [15][16][17]137 These and more recent studies [18][19][20][21][22][23] provide strong clinical support for the prometastatic function of heparanase. Subsequent studies provided compelling evidence that ties heparanase levels with all steps of tumor formation including tumor initiation, angiogenesis, growth, metastasis, and chemoresistance.…”

Section: Introductionmentioning

confidence: 85%

Heparanase—A single protein with multiple enzymatic and nonenzymatic functions

Vlodavsky,

Kayal,

Hilwi

et al. 2023

Proteoglycan Research

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Heparanase (Hpa1) is expressed by tumor cells and cells of the tumor microenvironment and functions extracellularly to remodel the extracellular matrix (ECM) and regulate the bioavailability of ECM‐bound factors, augmenting, among other effects, gene transcription, autophagy, exosome formation, and heparan sulfate (HS) turnover. Much of the impact of heparanase on tumor progression is related to its function in mediating tumor‐host crosstalk, priming the tumor microenvironment to better support tumor growth, metastasis, and chemoresistance. The enzyme appears to fulfill some normal functions associated, for example, with vesicular traffic, lysosomal‐based secretion, autophagy, HS turnover, and gene transcription. It activates cells of the innate immune system, promotes the formation of exosomes and autophagosomes, and stimulates signal transduction pathways via enzymatic and nonenzymatic activities. These effects dynamically impact multiple regulatory pathways that together drive tumor growth, dissemination, and drug resistance as well as inflammatory responses. The emerging premise is that heparanase expressed by tumor cells, immune cells, endothelial cells, and other cells of the tumor microenvironment is a key regulator of the aggressive phenotype of cancer, an important contributor to the poor outcome of cancer patients and a valid target for therapy. So far, however, antiheparanase‐based therapy has not been implemented in the clinic. Unlike heparanase, heparanase‐2 (Hpa2), a close homolog of heparanase (Hpa1), does not undergo proteolytic processing and hence lacks intrinsic HS‐degrading activity, the hallmark of heparanase. Hpa2 retains the capacity to bind heparin/HS and exhibits an even higher affinity towards HS than heparanase, thus competing for HS binding and inhibiting heparanase enzymatic activity. It appears that Hpa2 functions as a natural inhibitor of Hpa1 regulates the expression of selected genes that maintain tissue hemostasis and normal function, and plays a protective role against cancer and inflammation, together emphasizing the significance of maintaining a proper balance between Hpa1 and Hpa2.

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Section: Introductionmentioning

confidence: 85%

Heparanase—A single protein with multiple enzymatic and nonenzymatic functions

Vlodavsky,

Kayal,

Hilwi

et al. 2023

Proteoglycan Research

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Heparanase-The Message Comes in Different Flavors

Ilan

Bhattacharya

Barash

et al. 2020

Advances in Experimental Medicine and Biology

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Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

Liu

Sheng

Shuai

et al. 2018

WJG

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AIMTo detect the mechanisms of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC).METHODSSpecimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival (OS) and relapse-free survival (RFS) of GC patients were estimated by the Kaplan-Meier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot.RESULTSH. pylori infection was observed in 70 of 99 patients with GC (70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK (P < 0.05); HPA expression was relevant to MAPK expression (P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing (P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases (P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth.CONCLUSIONH. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

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Significance of heparanase in metastatic lymph nodes of cervical squamous cell cancer

Cited by 3 publications

References 30 publications

Heparanase—A single protein with multiple enzymatic and nonenzymatic functions

Heparanase—A single protein with multiple enzymatic and nonenzymatic functions

Heparanase-The Message Comes in Different Flavors

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

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