Heparanase mechanisms of melanoma metastasis to the brain: Development and use of a brain slice model.
Heparanase (HPSE-1) is an endo-beta-D-glucuronidase that cleaves heparan sulfate (HS) chains of proteoglycans (HSPG), and its expression has been associated with increased cell growth, invasion, and angiogenesis of tumors as well as with embryogenesis and tissue development. Since metastatic cancer cells express HPSE-1, we have developed an orthotopic brain slice model to study HPSE-1 involvement in brain-metastatic melanoma. This model allows for the characterization of tumor cell invasion at both quantitative and qualitative levels. Brain-metastatic melanoma cells (B16B15b) showed augmenting levels of HPSE-1 protein expression in a time-dependent manner. Secondly, B16B15b cells pre-treated with HPSE-1 showed a significant increase in the number of cells that invaded into the brain tissue. Finally, HPSE-1 exposure-augmented invasion depth in brain sections by brain-metastatic melanoma cells. We concluded that applying this brain slice model can be beneficial to investigate HPSE-1- related in vivo modalities in brain-metastatic melanoma and brain invasion in general. These results also further emphasize the potential relevance of using this model to design therapies for controlling this type of cancer by blocking HPSE-1 functionality.
Murry
Brian P
BP
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University at Baton Rouge, Baton Rouge, Louisiana 70803, USA.
Blust
Bryan E
BE
Singh
Amandip
A
Foster
Timothy P
TP
Marchetti
Dario
D
D000818:Animals; D001921:Brain; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary*; D045744:Cell Line, Tumor; D005260:Female; D005966:Glucuronidase / Q000378:metabolism* / Q000494:pharmacology*; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D046509:Tissue Culture Techniques; D000099175:Heparanase
D005966:Glucuronidase; D000099175:Heparanase