Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

Abstract

Glioblastoma is the most common and fatal type of primary brain tumors featured with hyperplastic blood vessels. Here, we performed meta-analyses of published data and established a correlation between high TIP-1 expression levels and the poor prognosis of glioblastoma patients. Next, we explored the biological relevance of TIP-1 expression in the pathogenesis of glioblastoma. By using orthotopic and heterotopic mouse models of human glioblastomas, this study has characterized TIP-1 as one contributing factor to the tumor-driven angiogenesis. In vitro and in vivo functional assays, along with biochemical analyses with microarrays and antibody arrays, have demonstrated that TIP-1 utilizes multiple pathways including modulating fibronectin gene expression and uPA protein secretion, to establish or maintain a pro-angiogenic microenvironment within human glioblastoma. In conclusion, this work supports the hypothesis that TIP-1 represents a novel prognostic biomarker and a therapeutic target of human glioblastoma.

Fluorescence-guided resection of experimental malignant glioma using cetuximab-IRDye 800CW

“…These results suggest that the increase in vessel density within the U-87MG tumours led to relatively higher fluorescence due to a higher blood-pool volume found within these tumours. The greater vessel density observed in the U-87MG tumours is consistent with similar studies evaluating vascularity and anti-angiogenic treatments (28–30). However, the average TBR between the cell lines was not significantly ( P =0.35) different at day 11.…”

Recent advance in molecular angiogenesis in glioblastoma: the challenge and hope for anti-angiogenic therapy

“…TIP-1 gene knock-down could delay tumor growth and decrease microvascular density, by depleting some related cytokine factors secreted by the D54 GBM cells, such as uPA, TSG14, IGFBP1 and IGFBP3 [56]. Vasculogenic mimicry (VM) plays a vital role in tumor development and cell proliferation.…”

PDZ Domain Recognition: Insight from Human Tax-Interacting Protein 1 (TIP-1) Interaction with Target Proteins

“…PDZ domains regulate essential functions such as the clustering of ion channels, protein targeting, membrane expression of receptors, cell polarity, and cell-cell communications [ 23 , 24 , 25 , 26 ]. Because PDZ-containing proteins interact with many proteins within a cell and are involved in several diseases [ 27 , 28 , 29 ], investigation of the mechanisms of PDZ domain-mediated protein-protein interactions is important for understanding the biological functions of PDZ domains and consequently for the possible design of new therapeutics.…”