Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC):: Attenuation C18-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis

被引:138
作者
Karahatay, Serdar
Thomas, Kesha
Koybasi, Serap
Senkal, Can E.
ElOjeimy, Saeed
Liu, Xiang
Bielawski, Jacek
Day, Terry A.
Gillespie, M. Boyd
Sinha, Debaiyoti
Norris, James S.
Hannun, Yusuf A.
Ogretmen, Besim
机构
[1] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
[2] Med Univ S Carolina, Head & Neck Surg, Dept Otolaryngol, Charleston, SC 29425 USA
[3] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA
[4] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA
[5] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA
[6] Gulhane Mil Med Acad, Dept Otolaryngol, Ankara, Turkey
关键词
ceramide; ceramide synthase; longevity assurance gene (LASS); head and neck cancer; lymphovascular spread; nodal metastasis; clinical markers;
D O I
10.1016/j.canlet.2007.06.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
It has been documented previously that defects in the generation of C-18-ceramide, a product of ceramide synthase 1 (CerS1), also known as longevity assurance gene 1 (hLASS1), play important roles in the pathogenesis and/or progression of HNSCC. However, whether altered levels of ceramide generation in HNSCC tumors have any clinical relevance remains unknown. In this study, the levels of endogenous ceramides were measured in tumor tissues of 45 HNSCC patients as compared to their normal tissues using high-pressure liquid chromatography/mass spectrometry (LC/MS), and then possible link between ceramide levels and the clinical parameters of HNSCC were examined. The data showed that the levels of C-16-, C-24-, C-24:1-ceramides were significantly elevated in the majority of tumor tissues compared to their normal tissues, while the levels of only C-18-ceramide were significantly decreased in HNSCC tumors, especially in tumor tissues of male patients. Importantly, it was also shown here that decreased Cls-ceramide levels in HNSCC tumor tissues were significantly associated with the higher incidences of lymphovascular invasion, and pathologic nodal metastasis. Importantly, attenuation of C-18-ceramide was also positively linked to the higher overall stages of the primary HNSCC tumors. Therefore, these data suggest, for the first time, that the defects in the generation/accumulation of C-18-ceramide might have important clinical roles in HNSCC, especially in lymphovascular invasion and nodal disease. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:101 / 111
页数:11
相关论文
共 58 条
[41]   Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells [J].
Rossi, MJ ;
Sundararaj, K ;
Koybasi, S ;
Phillips, MS ;
Szulc, ZM ;
Bielawska, A ;
Day, TA ;
Obeid, LM ;
Hannun, YA ;
Ogretmen, B .
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 2005, 132 (01) :55-62
[42]   Targeting sphingosine-I-phosphate for cancer therapy [J].
Sabbadini, R. A. .
BRITISH JOURNAL OF CANCER, 2006, 95 (09) :1131-1135
[43]  
SCHNEIDER B, IN PRESS J VOICE
[44]   Sphingolipids as modulators of cancer cell death:: Potential therapeutic targets [J].
Segui, Bruno ;
Andrieu-Abadie, Nathalie ;
Jaffrezou, Jean-Pierre ;
Benoist, Herve ;
Levade, Thierry .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2006, 1758 (12) :2104-2120
[45]   Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas [J].
Senkal, Can E. ;
Ponnusamy, Suriyan ;
Rossi, Michael J. ;
Bialewski, Jacek ;
Sinha, Debijyati ;
Jiang, James C. ;
Jazwinski, S. Michal ;
Hannun, Yusuf A. ;
Ogretmen, Besim .
MOLECULAR CANCER THERAPEUTICS, 2007, 6 (02) :712-722
[46]   Potent antitumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo [J].
Senkal, Can E. ;
Ponnusamy, Suriyan ;
Rossi, Michael J. ;
Sundararaj, Kamala ;
Szulc, Zdzislaw ;
Bielawski, Jacek ;
Bielawska, Alicja ;
Meyer, Mario ;
Cobanoglu, Bengu ;
Koybasi, Serap ;
Sinha, Debajyoti ;
Day, Terry A. ;
Obeid, Lina M. ;
Hannun, Yusuf A. ;
Ogretmen, Besim .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 317 (03) :1188-1199
[47]   Analysis of treatment results for base of tongue cancer [J].
Sessions, DG ;
Lenox, J ;
Spector, GJ ;
Chao, C ;
Chaudry, OA .
LARYNGOSCOPE, 2003, 113 (07) :1252-1261
[48]   Analysis of treatment results for floor-of-mouth cancer [J].
Sessions, DG ;
Spector, GJ ;
Lenox, J ;
Parriott, S ;
Haughey, B ;
Chao, C ;
Marks, J ;
Perez, C .
LARYNGOSCOPE, 2000, 110 (10) :1764-1772
[49]   Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas [J].
Shingaki, S ;
Takada, M ;
Sasai, K ;
Bibi, R ;
Kobayashi, T ;
Nomura, T ;
Saito, C .
AMERICAN JOURNAL OF SURGERY, 2003, 185 (03) :278-284
[50]  
Spiegel S, 2003, BIOCHEM SOC T, V31, P1216