Crosstalk between VEGF and novel angiogenic protein regulates tumor angiogenesis and contributes to aggressiveness of breast carcinoma

Belugali Nataraj, N. and Bharathi P. Salimath (2013) Crosstalk between VEGF and novel angiogenic protein regulates tumor angiogenesis and contributes to aggressiveness of breast carcinoma. Cellular Signalling, 25 (1). pp. 277-294.

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Official URL: http://doi.org/10.1016/j.cellsig.2012.09.013

Abstract

We have identified and characterized a novel proangiogenic glycoprotein (NAP) with molecular weight of 67. kDa from synovial fluid of rheumatoid arthritis patients. Proteomic analysis of the protein revealed 29% sequence coverage with maximum identity for human retinoblastoma binding protein 2. N-terminal amino acid sequence showed no identity to recently discovered protein sequences. NAP was also identified in both normal and tumor cell lines by Western blotting. NAP is a permeability factor as verified by miles permeability assay. The proangiogenic potential of NAP was identified using shell less CAM, rat cornea and tumor on CAM assays. NAP induces expression of VEGF and Flt-1 gene as verified by promoter reporter gene analysis. Further NAP induces proliferation of endothelial cells and formation of tube like structures. NAP is also involved in migration and invasion of tumor cells. Clinical data revealed the presence of NAP in breast cancer biopsies. We have developed monoclonal antibody (mAb), and specific ELISA, which confirmed the presence of NAP in the cytosol of tumor cells. The mAb effect was evaluated with established angiogenic assays. Further, we investigated the detailed mechanism by which NAP induces angiogenesis. NAP is phosphorylated by VEGF induced activation of MAPK and JNK pathways through VEGFR2 phosphorylation. NAP involves JNK pathway predominantly with further activation of NFκB in downstream processing of VEGF activation. Together these findings establish that NAP displays angiogenic properties and promotes efficient neovascularization both in vitro and in vivo models. These observations suggest that anti-NAP-mAb can be targeted for antiangiogenic therapy of cancer.

Item Type: Article
Uncontrolled Keywords: article, human, human tissue, priority journal, animal experiment, animal model, controlled study, drug efficacy, nonhuman, rat, adult, aged, Animals, enzyme inhibition, Rats, female, in vitro study, Female, Humans, nucleotide sequence, Cell Line, molecular weight, in vivo study, cell migration, Cell Movement, cell proliferation, human cell, mouse, Neovascularization, Pathologic, protein expression, treatment response, Tumor, Vascular Endothelial Growth Factor A, Genetic, Breast Neoplasms, vasculotropin, Signal Transduction, tumor cell line, Rattus, proteomics, Amino Acid Sequence, Molecular Sequence Data, Promoter Regions, rheumatoid arthritis, Phosphorylation, protein phosphorylation, immunoglobulin enhancer binding protein, NF-kappa B, amino acid sequence, protein analysis, angiogenesis, vasculotropin receptor 1, enzyme activation, cell invasion, Antibodies, endothelium cell, Human Umbilical Vein Endothelial Cells, stress activated protein kinase, enzyme regulation, angiogenic protein, Proteomics, Monoclonal, monoclonal antibody, synovial fluid, amino terminal telopeptide, Angiogenic Proteins, breast carcinogenesis, breast carcinoma, Cytosol, JNK Mitogen-Activated Protein Kinases, mitomycin C, reporter gene, retinoblastoma binding protein 2, Retinoblastoma-Binding Protein 2, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2, vasculotropin receptor 2
Subjects: B Life Science > Biotechnology
Divisions: Department of > Biotechnology
Depositing User: Arshiya Kousar
Date Deposited: 12 Sep 2019 07:32
Last Modified: 21 Sep 2019 09:48
URI: http://eprints.uni-mysore.ac.in/id/eprint/8054

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