Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy

Zhang, Jun; Yang, Jue; Han, Xiao‐Jian; Zhao, Zhenze; Du, Ling; Yu, Tong; Wang, Hui-Ju

doi:10.3892/ol.2012.703

Cited by 10 publications

(7 citation statements)

References 17 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, it was revealed that positive expression of HPA was able to predict the malignancy of GC due to its correlation with lymphatic metastasis and invasive depth. Beyond that, positive expression of HPA was a poor prognostic factor for overall survival and relapse-free survival compared with HPA negative cases, which was consistent with previously published reports[ 52 ]. Especially in GC patients with an obvious H. pylori infection, HPA positive expression indicated a poorer prognosis both in overall survival and in relapse-free survival, which illustrates that HPA is an important factor for the prediction of prognosis and relapse of GC and that H. pylori infection leads to an increase of HPA expression, which can worsen the prognosis of GC and make recurrence more likely.…”

Section: Discussionsupporting

confidence: 92%

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

Liu

Sheng

Shuai

et al. 2018

WJG

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

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

Liu

Sheng

Shuai

et al. 2018

WJG

View full text Add to dashboard Cite

show abstract

“…The present study was based on previous investigations of a heparanase MAP vaccination strategy (18)(19)(20)(21)(22), with the establishment of a method to induce a high-titer humoral immune response (23). To achieve the inhibition of TNF-α, internet software was used to predict the TNF-α B-cell epitope and an optimized immunization strategy (MAP + T cell epitope peptide) was used to induce high titers of antibody in vivo.…”

Section: Discussionmentioning

confidence: 99%

Prediction and identification of B-cell epitopes for tumor necrosis factor-α

Zhang

Cui

et al. 2017

Molecular Medicine Reports

Self Cite

View full text Add to dashboard Cite

The aim of the present study was to predict and identify B‑cell epitopes for mouse tumor necrosis factor‑α (mTNF‑α). DNAStar and BcePred software were used to predict B‑cell epitopes for mTNF‑α. A predicted eight‑branch multiple antigenic polypeptide (MAP) was synthesized and used to immunize BALB/c mice, combined with a promiscuous helper interleukin‑1β epitope (VQGEESNDK, amino acids 163‑171). The serum titer was measured. The specificity and avidity were determined by western blotting and indirect enzyme‑linked immunosorbent assay (ELISA). Amino acids 54‑65 (MAP1) and 78‑92 (MAP2) of mTNF‑α were predicted as most likely to be B‑cell epitopes. Dynamic monitoring of antibody concentration demonstrated that MAP1 and MAP2 may induce the production of specific antibodies with a higher antibody level for MAP2. Furthermore, MAP1 and MAP2 were confirmed to induce mTNF‑α‑specific antibodies by western blotting. Indirect ELISA was used to confirm that MAP2 had the highest affinity with commercial anti‑mTNF‑α antibody. Amino acids 54‑65 and 78‑94 of mTNF‑α are B‑cell epitopes, wherein amino acids 78‑94 have the strongest immunogenicity. The present study provides a theoretical basis for further research into the mTNF‑α polypeptide antibody and a B‑cell MAP vaccine.

show abstract

“…In light of the reported anti-inflammatory effects of heparin (Young, 2008), increased levels of highly sulfated, “heparin-resembling” HS fragments, which are constantly present in Hpa-tg , as compared to wt mice (Escobar Galvis et al, 2007b; Li et al, 2005), may offer an explanation for the inhibitory effects of continuous heparanase overexpression on neutrophils in these settings (Li et al, 2012a; Zhang et al, 2012a). In addition, it was noted that the thickness of the glycocalyx varies greatly between microvessels from different tissues: it is almost 3 times thinner in cremaster (systemic) microvessels endothelium than in pulmonary endothelium (Schmidt et al, 2012).…”

Section: Heparanase In Acute and Chronic Inflammationmentioning

confidence: 99%

Heparanase: From basic research to therapeutic applications in cancer and inflammation

Vlodavsky¹,

Singh²,

Boyango³

et al. 2016

Drug Resistance Updates

192

229

View full text Add to dashboard Cite

Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer. Heparanase neutralizing monoclonal antibodies block myeloma and lymphoma tumor growth and dissemination; this is attributable to a combined effect on the tumor cells and/or cells of the tumor microenvironment. In fact, 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 repertoire of the physiopathological activities of heparanase is expanding. Specifically, heparanase regulates gene expression, activates cells of the innate immune system, promotes the formation of exosomes and autophagosomes, and stimulates signal transduction pathways via enzymatic and non-enzymatic activities. These effects dynamically impact multiple regulatory pathways that together drive inflammatory responses, tumor survival, growth, dissemination and drug resistance; but in the same time, may fulfill some normal functions associated, for example, with vesicular traffic, lysosomal-based secretion, stress response, and heparan sulfate turnover. Heparanase is upregulated in response to chemotherapy in cancer patients and the surviving cells acquire chemoresistance, attributed, at least in part, to autophagy. Consequently, heparanase inhibitors used in tandem with chemotherapeutic drugs overcome initial chemoresistance, providing a strong rationale for applying anti-heparanase therapy in combination with conventional anti-cancer drugs. Heparin-like compounds that inhibit heparanase activity are being evaluated in clinical trials for various types of cancer. Heparanase neutralizing monoclonal antibodies are being evaluated in pre-clinical studies, and heparanase-inhibiting small molecules are being developed based on the recently resolved crystal structure of the heparanase protein. Collectively, the emerging premise is that heparanase expressed by tumor cells, innate immune cells, activated endothelial cells as well as other cells of the tumor microenvironment is a master regulator of the aggressive phenotype of cancer, an important contributor to the poor outcome of cancer patients and a prime target for therapy.

show abstract

Overexpression of heparanase multiple antigenic peptide 2 is associated with poor prognosis in gastric cancer: Potential for therapy

Cited by 10 publications

References 17 publications

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

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

Prediction and identification of B-cell epitopes for tumor necrosis factor-α

Heparanase: From basic research to therapeutic applications in cancer and inflammation

Contact Info

Product

Resources

About