Role of heparanase 2 (Hpa2) in gastric cancer

Liu, Jingjing; Knani, Ibrahim; Gross-Cohen, Miriam; Hu, Junbo; Wang, Sumin; Tang, Li; Ilan, Neta; Yang, Shiming; Vlodavsky, Israël

doi:10.1016/j.neo.2021.07.010

Cited by 11 publications

(32 citation statements)

References 62 publications

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“…The expression level of the HPSE2 gene is low in most malignant cell lines [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Likewise, RMPI-8226 cells expressed a very low, but detectable level of HPSE2 and there was no effect to electrical pulse and transfection with an empty plasmid.…”

Section: Resultsmentioning

confidence: 99%

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Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma

Ostrovsky

Beider

Magen

et al. 2023

Cells

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Multiple myeloma (MM) is a plasma cell malignancy that is accompanied by hypercalcemia, renal failure, anemia, and lytic bone lesions. Heparanase (HPSE) plays an important role in supporting and promoting myeloma progression, maintenance of plasma cell stemness, and resistance to therapy. Previous studies identified functional single nucleotide polymorphisms (SNPs) located in the HPSE gene. In the present study, 5 functional HPSE SNPs and 11 novel HPSE2 SNPs were examined. A very significant association between two enhancer (rs4693608 and rs4693084), and two insulator (rs4364254 and rs4426765) HPSE SNPs and primary paraskeletal disease (PS) was observed. SNP rs657442, located in intron 9 of the HPSE2 gene, revealed a significant protective association with primary paraskeletal disease and lytic bone lesions. The present study demonstrates a promoting (HPSE gene) and protective (HPSE2 gene) role of gene regulatory elements in the development of paraskeletal disease and bone morbidity. The effect of signal discrepancy between myeloma cells and normal cells of the tumor microenvironment is proposed as a mechanism for the involvement of heparanase in primary PS. We suggest that an increase in heparanase-2 expression can lead to effective suppression of heparanase activity in multiple myeloma accompanied by extramedullary and osteolytic bone disease.

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Section: Resultsmentioning

confidence: 99%

“…The role of Hpa2 in the development of cancer is not well understood. However, heparanase-2 inhibits heparanase enzymatic activity [ 23 ] and appears to function as a tumor suppressor [ 19 , 24 , 25 , 26 , 27 , 28 , 29 ]. The role of heparanase-2 in multiple myeloma has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma

Ostrovsky

Beider

Magen

et al. 2023

Cells

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“…Adding miR-10b-5p to gastric cancer cells and implanting them subcutaneously in mice inhibits the proliferation and migration of gastric cancer cells due to the upregulation of Tiam1 [ 89 ]. Mice overexpressing Hpa2 for gastric cancer cells produced smaller tumors and survived longer than control mice [ 90 ]. This mechanism is related to the increased phosphorylation of AMP-activated protein kinase (AMPK), a protein that is located in tumor suppressors.…”

Section: Discussionmentioning

confidence: 99%

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer

et al. 2022

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Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related deaths. Surgery remains the first-choice treatment. Chemotherapy is considered in the middle and advanced stages, but has limited success. Microspherule protein 1 (MCRS1, also known as MSP58) is a protein originally identified in the nucleus and cytoplasm that is involved in the cell cycle. High expression of MCRS1 increases tumor growth, invasiveness, and metastasis. The mechanistic relationships between MCSR1 and proliferation, apoptosis, angiogenesis, and epithelial–mesenchymal transition (EMT) remain to be elucidated. We clarified these relationships using immunostaining of tumor tissues and normal tissues from patients with gastric cancer. High MCRS1 expression in gastric cancer positively correlated with Ki-67, Caspase3, CD31, Fibronectin, pAKT, and pAMPK. The hazard ratio of high MCRS1 expression was 2.44 times that of low MCRS1 expression, negatively impacting patient survival.

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“…Of note, gastric cancer patients exhibiting high levels of HPSE-2 showed better survival rates (J. Liu et al, 2021). This is associated with increased phosphorylation of AMP-activated protein kinase (AMPK), a kinase located at the center of the tumor suppressor network.…”

Section: Hpse-2 Blocks Gastric Tumorigenesis By Enhancing Ampk Phosph...mentioning

confidence: 99%

“…Notably, the induction of HPSE-2 by MG132 appears to be mediated by AMPK, which was found to induce HPSE-2 expression, leading to attenuation of gastric tumorigenesis (J. Liu et al, 2021).…”

Section: Hpse-2 Blocks Gastric Tumorigenesis By Enhancing Ampk Phosph...mentioning

confidence: 99%

Potential roles of heparanase in cancer therapy: Current trends and future direction

Yang

Yuan

Zhou

et al. 2023

Journal Cellular Physiology

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Heparanase (HPSE; heparanase‐1) is an endo‐β‐glucuronidase capable of degrading the carbohydrate moiety of heparan sulfate proteoglycans, thus modulating and facilitating the remodeling of the extracellular matrix and basement membrane. HPSE activity is strongly associated with major human pathological complications, including but not limited to tumor progress and angiogenesis. Several lines of literature have shown that overexpression of HPSE leads to enhanced tumor growth and metastatic transmission, as well as poor prognosis. Gene silencing of HPSE or treatment of tumor with compounds that block HPSE activity are shown to remarkably attenuate tumor progression. Therefore, targeting HPSE is considered as a potential therapeutical strategy for the treatment of cancer. Intriguingly, recent findings disclose that heparanase‐2 (HPSE‐2), a close homolog of HPSE but lacking enzymatic activity, can also regulate antitumor mechanisms. Given the pleiotropic roles of HPSE, further investigation is in demand to determine the precise mechanism of regulating action of HPSE in different cancer settings. In this review, we first summarize the current understanding of HPSE, such as its structure, subcellular localization, and tissue distribution. Furthermore, we systematically review the pro‐ and antitumorigenic roles and mechanisms of HPSE in cancer progress. In addition, we delineate HPSE inhibitors that have entered clinical trials and their therapeutic potential.

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Role of heparanase 2 (Hpa2) in gastric cancer

Cited by 11 publications

References 62 publications

Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma

Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer

Potential roles of heparanase in cancer therapy: Current trends and future direction

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