Metabolomic characterization of experimental ovarian cancer ascitic fluid

被引:30
作者
Bharti, Santosh K. [1 ]
Wildes, Flonne [1 ]
Hung, Chien-Fu [2 ]
Wu, T. C. [2 ]
Bhujwalla, Zaver M. [1 ,3 ]
Penet, Marie-France [1 ,3 ]
机构
[1] Johns Hopkins Univ, Div Canc Imaging Res, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, 212 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA
关键词
Ovarian cancer; Ascitic fluid; Orthotopic tumor implantation; Metabolites; High-resolution proton NMR; Cancer cells; Conditioned culture media; MALIGNANT ASCITES; SPECTROSCOPY; METABOLITES; CELLS; SERUM;
D O I
10.1007/s11306-017-1254-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction Malignant ascites (MA) is a major cause of morbidity that occurs in 37% of ovarian cancer patients. The accumulation of MA in the peritoneal cavity due to cancer results in debilitating symptoms and extremely poor quality of life. There is an urgent unmet need to expand the understanding of MA to design effective treatment strategies, and to improve MA diagnosis. Objective Our purpose here is to contribute to a better characterization of MA metabolic composition in ovarian cancer. Method We determined the metabolic composition of ascitic fluids resulting from orthotopic growth of two ovarian cancer cell lines, the mouse ID8-vascular endothelial growth factor (VEGF)-Defb29 cell line and the human OVCAR3 cell line using high-resolution H-1 MRS. ID8VEGF-Defb29 tumors induce large volumes of ascites, while OVCAR3 tumors induce ascites less frequently and at smaller volumes. To better understand the factors driving he metabolic composition of the fluid, we characterized the metabolism of these ovarian cancer cells in culture by analyzing cell lysates and conditioned culture media with H-1 NMR. Results Distinct metabolite patterns were detected in ascitic fluid collected from OVCAR3 and ID8-VEGFDefb29 tumor bearing mice that were not reflected in the corresponding cell culture or conditioned medium. Conclusion High-resolution H-1 NMR metabolic markers of MA can be used to improve characterization and diagnosis of MA. Metabolic characterization of MA can provide new insights into how MA fluid supports cancer cell growth and resistance to treatment, and has the potential to identify metabolic targeting strategies to reduce or eliminate the formation of MA.
引用
收藏
页数:11
相关论文
共 24 条
[1]  
ADOSRAKU RK, 1994, J LIPID RES, V35, P1925
[2]  
Ammouri L, 2010, BIOL-TARGETS THER, V4, P103
[3]   Oncolytic virotherapy for malignant glioma: translating laboratory insights into clinical practice [J].
Auffinger, Brenda ;
Ahmed, Atique U. ;
Lesniak, Maciej S. .
FRONTIERS IN ONCOLOGY, 2013, 3
[4]   1H NMR spectroscopy of ascitic fluid:: discrimination between malignant and benign ascites and comparison of the results with conventional methods [J].
Bala, Lakshmi ;
Sharma, Abhinav ;
Yellapa, Radha Krishna ;
Roy, Raja ;
Choudhuri, G. ;
Khetrapal, C. L. .
NMR IN BIOMEDICINE, 2008, 21 (06) :606-614
[5]   Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts [J].
Beckonert, Olaf ;
Keun, Hector C. ;
Ebbels, Timothy M. D. ;
Bundy, Jacob G. ;
Holmes, Elaine ;
Lindon, John C. ;
Nicholson, Jeremy K. .
NATURE PROTOCOLS, 2007, 2 (11) :2692-2703
[6]   Metabolite Identification in NMR-based Metabolomics [J].
Bharti, Santosh Kumar ;
Roy, Raja .
CURRENT METABOLOMICS, 2014, 2 (03) :163-173
[7]   Quantitative 1H NMR spectroscopy [J].
Bharti, Santosh Kumar ;
Roy, Raja .
TRAC-TRENDS IN ANALYTICAL CHEMISTRY, 2012, 35 :5-26
[8]   Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of Vegf-A [J].
Conejo-Garcia, JR ;
Benencia, F ;
Coureges, MC ;
Kang, E ;
Mohamed-Hadley, A ;
Buckanovich, RJ ;
Holtz, DO ;
Jenkins, A ;
Na, HN ;
Zhang, L ;
Wagner, DS ;
Katsaros, D ;
Caroll, R ;
Coukos, G .
NATURE MEDICINE, 2004, 10 (09) :950-958
[9]   H-1 NMR Analysis of Cerebrospinal Fluid from Alzheimer's Disease Patients: An Example of a Possible Misinterpretation Due to Non-Adjustment of pH [J].
Cruz, Thomas ;
Balayssac, Stephane ;
Gilard, Veronique ;
Martino, Robert ;
Vincent, Christian ;
Pariente, Jeremie ;
Malet-Martino, Myriam .
METABOLITES, 2014, 4 (01) :115-128
[10]   Quantitating Metabolites in Protein Precipitated Serum Using NMR Spectroscopy [J].
Gowda, G. A. Nagana ;
Raftery, Daniel .
ANALYTICAL CHEMISTRY, 2014, 86 (11) :5433-5440