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Heparanase promotes...
Heparanase promotes glioma progression via enhancing CD24 expression
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- Barash, Uri (author)
- Rappaport Fac Med, TICC, Haifa, Israel
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- Spyrou, Argyris (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Liu, Pei (author)
- Shantou Univ, Med Coll, Shantou, Peoples R China
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- Vlodaysky, Euvgeni (author)
- Rambam Hlth Care Campus, Dept Pathol, Haifa, Israel
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- Zhu, Chenchen (author)
- Shantou Univ, Med Coll, Shantou, Peoples R China
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- Luo, Juanjuan (author)
- Shantou Univ, Med Coll, Shantou, Peoples R China
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- Su, Dongsheng (author)
- Shantou Univ, Med Coll, Shantou, Peoples R China
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- Ilhan, Neta (author)
- Rappaport Fac Med, TICC, Haifa, Israel
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- Forsberg Nilsson, Karin, 1963- (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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- Vlodaysky, Israel (author)
- Rappaport Fac Med, TICC, Haifa, Israel
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- Yang, Xiaojun (author)
- Shantou Univ, Med Coll, Shantou, Peoples R China
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(creator_code:org_t)
- 2019-05-14
- 2019
- English.
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In: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 145:6, s. 1596-1608
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Heparanase is an endo-beta-d-glucuronidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans. Compelling evidence tie heparanase levels with all steps of tumor formation including tumor initiation, growth, metastasis and chemo-resistance, likely involving augmentation of signaling pathways and gene transcription. In order to reveal the molecular mechanism(s) underlying the protumorigenic properties of heparanase, we established an inducible (Tet-on) system in U87 human glioma cells and applied gene array methodology in order to identify genes associated with heparanase induction. We found that CD24, a mucin-like cell adhesion protein, is consistently upregulated by heparanase and by heparanase splice variant devoid of enzymatic activity, whereas heparanase gene silencing was associated with decreased CD24 expression. This finding was further substantiated by a similar pattern of heparanase and CD24 immunostaining in glioma patients (Pearson's correlation; R = 0.66, p = 0.00001). Noteworthy, overexpression of CD24 stimulated glioma cell migration, invasion, colony formation in soft agar and tumor growth in mice suggesting that CD24 functions promote tumor growth. Likewise, anti-CD24 neutralizing monoclonal antibody attenuated glioma tumor growth, and a similar inhibition was observed in mice treated with a neutralizing mAb directed against L1 cell adhesion molecule (L1CAM), a ligand for CD24. Importantly, significant shorter patient survival was found in heparanase-high/CD24-high tumors vs. heparanase-high/CD24-low tumors for both high-grade and low-grade glioma (p = 0.02). Our results thus uncover a novel heparanase-CD24-L1CAM axis that plays a significant role in glioma tumorigenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- heparanase
- glioma
- CD24
- L1CAM
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Barash, Uri
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Spyrou, Argyris
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Liu, Pei
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Vlodaysky, Euvge ...
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Zhu, Chenchen
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Luo, Juanjuan
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show more...
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Su, Dongsheng
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Ilhan, Neta
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Forsberg Nilsson ...
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Vlodaysky, Israe ...
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Yang, Xiaojun
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Uppsala University