Abstract
The molecular pathways involved in neovascularization of regenerating tissues and tumor angiogenesis resemble each other. However, the regulatory mechanisms of neovascularization under neoplastic circumstances are unbalanced leading to abnormal protein expression patterns resulting in the formation of defective and often abortive tumor vessels. Because gliomas are among the most vascularized tumors, we compared the protein expression profiles of proliferating vessels in glioblastoma with those in tissues in which physiological angiogenesis takes place. By using a combination of laser microdissection and LTQ Orbitrap mass spectrometry comparisons of protein profiles were made. The approach yielded 29 and 12 differentially expressed proteins for glioblastoma and endometrium blood vessels, respectively. The aberrant expression of five proteins, i.e. periostin, tenascin-C, TGF-beta induced protein, integrin alpha-V, and laminin subunit beta-2 were validated by immunohistochemistry. In addition, pathway analysis of the differentially expressed proteins was performed and significant differences in the usage of angiogenic pathways were found. We conclude that there are essential differences in protein expression profiles between tumor and normal physiological angiogenesis.
Highlights
Neovascularization is a complex process taking place under physiological and pathological circumstances
In order to identify proteins that are expressed in tumor angiogenesis, comparisons with protein profiles of blood vessels in which active normal angiogenesis take place are necessary
Out of the 152 differentially expressed proteins 29 were found in the GBM blood vessel group (Table IIIA) whereas 12 were found in the endometrium blood vessel group (Table IIIB)
Summary
Neovascularization is a complex process taking place under physiological and pathological circumstances. There is large overlap in the cellular components, regulatory factors, and signaling mechanisms acting in the angiogenic process of regeneration, embryonic development, and tumor vascularization [1] In both physiological and pathological neovascularization signaling mechanisms, growth factors and their receptors, cell adhesion molecules and their specific extracellular matrix ligands take part [2]. The identification of differences in protein expression patterns are of paramount clinical importance: in some situations the formation of new blood vessels should be stimulated, whereas in others the main goal is to repress neovascularization. To this end, we microdissected the blood vessels from GBM and proliferating endometrium by using laser capture microdissection. A selection of differentially expressed proteins was validated by immunohistochemistry
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