Heparanase and Heparanase-2: Function, Regulation, Signaling, and Disease
A special issue of Cells (ISSN 2073-4409).
Deadline for manuscript submissions: 31 August 2025 | Viewed by 84
Special Issue Editors
Interests: heparanase; tumor microenvironment; extracellular matrix; tumor progression; metastasis
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Heparanase (Hpa1) is expressed by tumor cells and cells of the tumor microenvironment and functions extracellularly to remodel the extracellular matrix (ECM) and regulate the bioavailability of ECM-bound factors, augmenting, among other effects, gene transcription, autophagy, exosome formation, and heparan sulfate (HS) turnover. Much of the impact of heparanase on tumor progression is related to its function in mediating tumor–host crosstalk and priming the tumor microenvironment to better support tumor growth, metastasis, and chemoresistance. The emerging premise is that heparanase, expressed by tumor cells, immune cells, endothelial cells, and other cells of the tumor microenvironment, is a key regulator of the aggressive phenotype of cancer, an important contributor to the poor outcome of cancer patients, and a valid target for therapy. So far, however, anti-heparanase-based therapy has not been implemented in the clinic. Unlike heparanase, heparanase-2 (Hpa2), a close homolog of heparanase (Hpa1), does not undergo proteolytic processing and hence lacks intrinsic HS-degrading activity, the hallmark of heparanase. Hpa2 retains the capacity to bind heparin/HS and exhibits an even higher affinity for HS than heparanase, thus competing for HS binding and inhibiting heparanase enzymatic activity. It appears that Hpa2 functions as a natural inhibitor of Hpa1, regulates the expression of selected genes that maintain tissue hemostasis and normal function, and plays a protective role against cancer and inflammation, together emphasizing the significance of maintaining a proper Hpa1/Hpa2 ratio.
We warmly invite researchers in this field to submit their work to this Special Issue. Both original research articles and comprehensive reviews are welcome.
Prof. Dr. Israël Vlodavsky
Prof. Dr. Jin-Ping Li
Guest Editors
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Keywords
- heparanase (Hpa1)
- heparanase-2 (Hpa2)
- tumor microenvironment
- extracellular matrix
- tumor progression
- tumor suppression
- metastatic niche
- glycocalyx
- immune cells
- inflammation
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