Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype in bladder cancer
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Venkatrao Vantaku1,*, Sri Ramya Donepudi2,*, Chandrashekar R. Ambati2,*, Feng Jin2, Vasanta Putluri2, Khoa Nguyen3, Kimal Rajapakshe1, Cristian Coarfa1,2, Venkata Lokesh Battula3, Yair Lotan4 and Nagireddy Putluri1,2
1Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA
2Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA
3Section of Molecular Hematology and Therapy, Department of Leukemia, and Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4Department of Urology, University of Texas Southwestern, Dallas, TX, USA
*These authors have contributed equally to this work
Nagireddy Putluri, email: [email protected]
Keywords: bladder cancer; ganglioside GD2; lipid metabolism; EMT
Received: June 27, 2017 Accepted: August 04, 2017 Published: September 16, 2017
High-grade Bladder Cancer (BLCA) represents the most aggressive and treatment-resistant cancer that renders the patients with poor survival. However, only a few biomarkers have been identified for the detection and treatment of BLCA. Recent studies show that ganglioside GD2 can be used as cancer biomarker and/or therapeutic target for various cancers. Despite its potential relevance in cancer diagnosis and therapeutics, the role of GD2 is unknown in BLCA. Here, we report for the first time that high-grade BLCA tissues and cell lines have higher expression of GD2 compared to low-grade by high-resolution Mass Spectrometry. The muscle invasive UMUC3 cell line showed high GD2, mesenchymal phenotype, and cell proliferation. Besides, we have shown the cancer stem cells (CSC) property (CD44hiCD24lo) of GD2+ UMUC3 and J82 cells. Also, the evaluation of lipid metabolism in GD2+ BLCA cell lines revealed higher levels of Phosphatidylinositol (PI), Phosphatidic acid (PA), Cardiolipin (CL) and lower levels of Phosphatidylserine (PS), plasmenyl-phosphatidylethanolamines (pPE), plasmenyl-phosphocholines (pPC), sphingomyelins (SM), triglycerides (TGs) and N-Acetylneuraminic acid. These findings are significantly correlated with the tissues of BLCA patients. Based on this evidence, we propose that GD2 may be used as an effective diagnostic and therapeutic target for aggressive BLCA.
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