TY - JOUR
T1 - Targeting Heparanase in Cancer
T2 - Inhibition by Synthetic, Chemically Modified, and Natural Compounds
AU - Mohan, Chakrabhavi Dhananjaya
AU - Hari, Swetha
AU - Preetham, Habbanakuppe D.
AU - Rangappa, Shobith
AU - Barash, Uri
AU - Ilan, Neta
AU - Nayak, S. Chandra
AU - Gupta, Vijai K.
AU - Basappa,
AU - Vlodavsky, Israel
AU - Rangappa, Kanchugarakoppal S.
PY - 2019/5/31
Y1 - 2019/5/31
N2 - Heparanase is an endoglycosidase involved in remodeling the extracellular matrix and thereby in regulating multiple cellular processes and biological activities. It cleaves heparan sulfate (HS) side chains of HS proteoglycans into smaller fragments and hence regulates tissue morphogenesis, differentiation, and homeostasis. Heparanase is overexpressed in various carcinomas, sarcomas, and hematological malignancies, and its upregulation correlates with increased tumor size, tumor angiogenesis, enhanced metastasis, and poor prognosis. In contrast, knockdown or inhibition of heparanase markedly attenuates tumor progression, further underscoring the potential of anti-heparanase therapy. Heparanase inhibitors were employed to interfere with tumor progression in preclinical studies, and selected heparin mimetics are being examined in clinical trials. However, despite tremendous efforts, the discovery of heparanase inhibitors with high clinical benefit and minimal adverse effects remains a therapeutic challenge. This review discusses the key roles of heparanase in cancer progression focusing on the status of natural, chemically modified, and synthetic heparanase inhibitors in various types of malignancies. Biological Sciences; Glycobiology; Molecular Biology; Cell Biology
AB - Heparanase is an endoglycosidase involved in remodeling the extracellular matrix and thereby in regulating multiple cellular processes and biological activities. It cleaves heparan sulfate (HS) side chains of HS proteoglycans into smaller fragments and hence regulates tissue morphogenesis, differentiation, and homeostasis. Heparanase is overexpressed in various carcinomas, sarcomas, and hematological malignancies, and its upregulation correlates with increased tumor size, tumor angiogenesis, enhanced metastasis, and poor prognosis. In contrast, knockdown or inhibition of heparanase markedly attenuates tumor progression, further underscoring the potential of anti-heparanase therapy. Heparanase inhibitors were employed to interfere with tumor progression in preclinical studies, and selected heparin mimetics are being examined in clinical trials. However, despite tremendous efforts, the discovery of heparanase inhibitors with high clinical benefit and minimal adverse effects remains a therapeutic challenge. This review discusses the key roles of heparanase in cancer progression focusing on the status of natural, chemically modified, and synthetic heparanase inhibitors in various types of malignancies. Biological Sciences; Glycobiology; Molecular Biology; Cell Biology
KW - Biological Sciences
KW - Cell Biology
KW - Glycobiology
KW - Molecular Biology
UR - http://www.scopus.com/inward/record.url?scp=85066327367&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2019.04.034
DO - 10.1016/j.isci.2019.04.034
M3 - Review article
C2 - 31103854
AN - SCOPUS:85066327367
SN - 2589-0042
VL - 15
SP - 360
EP - 390
JO - iScience
JF - iScience
ER -
