TY - JOUR
T1 - Expression of ganglioside GD2, reprogram the lipid metabolism and EMT phenotype in bladder cancer
AU - Vantaku, Venkatrao
AU - Donepudi, Sri Ramya
AU - Ambati, Chandrashekar R.
AU - Jin, Feng
AU - Putluri, Vasanta
AU - Nguyen, Khoa
AU - Rajapakshe, Kimal
AU - Coarfa, Cristian
AU - Battula, Venkata Lokesh
AU - Lotan, Yair
AU - Putluri, Nagireddy
N1 - Funding Information:
This research was fully supported by American cancer society (ACS) award 127430-RSG-15-105-01-CNE (N.P.), NIH/NCI R01CA220297 (N.P); partially supported by the following grants: NIH U01 CA167234 (A.S.K.), UO1 CA179674 (A.S.K.) and RP150451 (A.S.K.). This project was also supported by the Metabolomics core at Baylor College of Medicine with funding from the NIH (P30 CA125123), CPRIT Proteomics and Metabolomics Core Facility (D.P.E.), (RP120092), and Dan L. Duncan Cancer Center. This project was also supported by the Agilent Technologies Center of Excellence in Mass Spectrometry at Baylor College of Medicine, as well as funds from the Diana Helis Henry Medical Research Foundation, Alkek Center for Molecular Discovery.
Publisher Copyright:
© Vantaku et al.
PY - 2017
Y1 - 2017
N2 - High-grade Bladder Cancer (BLCA) represents the most aggressive and treatmentresistant 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.
AB - High-grade Bladder Cancer (BLCA) represents the most aggressive and treatmentresistant 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.
KW - Bladder cancer
KW - EMT
KW - Ganglioside GD2
KW - Lipid metabolism
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U2 - 10.18632/oncotarget.21038
DO - 10.18632/oncotarget.21038
M3 - Article
C2 - 29221154
AN - SCOPUS:85033389050
SN - 1949-2553
VL - 8
SP - 95620
EP - 95631
JO - Oncotarget
JF - Oncotarget
IS - 56
ER -