High heparanase activity in multiple myeloma is associated with elevated microvessel density

Area of Science:

• Oncology
• Biochemistry
• Cancer Biology

Background:

• Heparanase enzyme cleaves heparan sulfate, influencing tumor growth, metastasis, and angiogenesis.
• Multiple myeloma is characterized by high syndecan-1 expression and vascularized bone marrow aggregates.
• The role of heparanase in the myeloma microenvironment requires further investigation.

Purpose of the Study:

• To analyze the activity, expression, and function of heparanase in multiple myeloma patients.
• To determine the correlation between heparanase activity and tumor vascularity in myeloma.
• To assess the potential of heparanase as a therapeutic target in multiple myeloma.

Main Methods:

• Analysis of heparanase activity in bone marrow and peripheral blood plasma from myeloma patients.
• Immunohistochemical staining for heparanase expression in tumor cells.
• Assessment of microvessel density in bone marrow biopsies.
• Xenograft studies in SCID mice using heparanase-transfected myeloma cells.

Main Results:

• 86% of 100 myeloma patients showed heparanase activity in bone marrow plasma, with 42 having high activity.
• Heparanase activity was significantly higher in bone marrow compared to peripheral blood.
• High heparanase activity strongly correlated with increased microvessel density (78.96 vessels/mm(2) vs. 25.03 vessels/mm(2)).
• Myeloma tumors in mice exhibited higher vascularity when expressing heparanase.

Conclusions:

• Heparanase is predominantly active within the bone marrow microenvironment in multiple myeloma.
• Heparanase expression directly promotes tumor angiogenesis and microvessel density in myeloma.
• Targeting heparanase may represent a promising therapeutic approach for multiple myeloma.