Identifier

etd-07132005-134343

Degree

Master of Science (MS)

Department

Biomedical and Veterinary Medical Sciences - Comparative Biomedical Sciences

Document Type

Thesis

Abstract

This thesis focuses on the study of heparanase which is an enzyme involved as a molecular determinant of cancer metastasis. The purpose of this study was to first quantitate heparanase mRNA levels in both normal and tumorigenic samples from the same tissue specimen. Laser capture microdissection was used in the isolation and extraction of melanoma cell populations from normal tissue. There was a 29 fold upregulation of heparanase expression, detected by real-time PCR, in metastatic melanoma of the lung in comparison to normal lung tissue in mice. Immunohistochemistry (IHC) showed stronger staining in human metastatic melanoma when compared to primary melanoma tumors. IHC also showed a propensity for darker heparanase staining around blood vessels and vascular regions. These results further emphasized the importance of heparanase in invasive and angiogenic mechanisms in melanoma. Once heparanase was determined to be upregulated in melanoma tissue in vivo both at the mRNA and protein level, the next part of this thesis was directed to the development of an orthotopic brain slice model. A novel model that would provide a relatively efficient way to study the biological relevance and mechanisms involved in the invasive process of brain metastatic melanoma and the role that heparanase plays in this invasive process. We showed that this model could be used to determine invasion into brain tissue at both qualitative and quantitative levels. We showed that HPSE-1 augmented invasion of brain metastatic melanoma cells into brain tissue. We also showed that melanoma cells show a time dependent expression of heparanase while invading into brain tissue. Thus, we showed that heparanase is involved in cancer metastasis development and could have important implications in the development of potential drugs aimed to combat cancer metastasis.

Date

2005

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Dario Marchetti

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