This review focuses on present knowledge and recent development in the study of heparanase in cancer progression as well as on novel mechanisms by which heparanase regulates tumor metastasis and chemo-resistance.
Heparanase has been strongly associated with important pathological processes including inflammatory disease and tumor metastasis, through its ability to promote various cellular functions such as cell migration, invasion, adhesion, and cytokine release.
Although cancer cells use heparanase for tumor metastasis, favourable effects of heparanase have been reported in the management of Alzheimer's disease and diabetes.
Thus, examination of heparanase levels in the tumor metastases should be evaluated for most efficient precision medicine applying heparanase inhibitors.
Mammalian cells express a single functional heparanase, an endoglycosidase that cleaves heparan sulfate and thereby promotes tumor metastasis, angiogenesis, and inflammation.
We sought to evaluate the feasibility of HPA as a common TAA for magnetic resonance imaging (MRI) of tumor metastasis and its potential application in tumor molecular imaging.
Heparanase is a heparan sulfate degrading enzyme that cleaves heparan sulfate (HS) chains present on HS proteoglycans (HSPGs), and has been well characterized for its roles in tumor metastasis and inflammation.
This review focuses on recent developments in the field of heparanase regulation of cancer and inflammation, including the impact of heparanase on exosomes and autophagy, and novel mechanisms whereby heparanase regulates tumor metastasis, angiogenesis and chemoresistance.
Together, these results demonstrate that HGF/c-met can activate PI3K/Akt and downstream NF-κB signaling to promote HPA expression and subsequent tumor metastasis.
Here, we review current knowledge about heparanase and its involvement in tumor metastasis, with an emphasis on recent results from heparanase-targeted cancer immunotherapy studies.
These findings suggest that heparanase plays a unique dual role in tumor metastasis, facilitating tumor cell invasiveness and inducing VEGF C expression, thereby increasing the density of lymphatic vessels that mobilize metastatic cells.
Moreover, heparanase up-regulation was noted in an increasing number of primary human tumors, correlating with tumors larger in size, increased microvessel density, and reduced postoperative survival rate, implying that heparanase function is not limited to tumor metastasis.
N-acetylated glycol-split species of heparin, as well as heparanase gene silencing inhibit tumor metastasis, angiogenesis and inflammation in experimental animal models.
Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate chains on cell surfaces and in the extracellular matrix, activity that closely correlates with cell invasion, angiogenesis and tumor metastasis.
N-acetylated glycol-split species of heparin as well as siRNA heparanase gene silencing inhibit tumor metastasis and angiogenesis in experimental models.
In vitro studies were also performed to examine tumor invasion and to test the effects of heparanase inhibition, and in vivo studies were performed to examine tumor metastasis and prognosis.