Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2 synthesis in colon cancer cells

被引:286
作者
Accioly, Maria T. [1 ]
Pacheco, Patricia [2 ]
Maya-Monteiro, Clarissa M. [2 ]
Carrossini, Nina [1 ]
Robbs, Bruno K. [1 ]
Oliveira, Silvia S. [1 ]
Kaufmann, Cristiane [1 ]
Morgado-Diaz, Jose A. [1 ]
Bozza, Patricia T. [2 ]
Viola, Joao P. B. [1 ]
机构
[1] Natl Canc Inst, Div Cellular Biol, BR-20231050 Rio De Janeiro, RJ, Brazil
[2] Fiocruz MS, Inst Oswaldo Cruz, Lab Immunopharmacol, BR-21045900 Rio De Janeiro, Brazil
关键词
D O I
10.1158/0008-5472.CAN-07-1999
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Lipid bodies (lipid droplets) are emerging as dynamic organelles involved in lipid metabolism and inflammation. Increased lipid body numbers have been described in tumor cells; however, its functional significance in cancer has never been addressed. Here, we showed increased number of lipid bodies in tumor tissues from patients with adenocarcinoma of colon submitted to surgical resection when compared with an adjacent normal tissue. Accordingly, increased numbers of lipid bodies were observed in human colon adenocarcinoma cell lines and in a H-rasV12-transformed intestinal epithelial cell line (IEC-6 H-rasV12) compared with nontransformed IEC-6 cells. The functions of lipid bodies in eicosanoid synthesis in cancer cells were investigated. CACO-2 cells have increased expression of cyclooxygenase-2 (COX-2) when compared with IEC-6 cells. We showed by immunolocalization that, in addition to perinuclear stain, COX-2 and prostaglandin E (PGE) synthase present punctate cytoplasmic localizations that were concordant with adipose differentiation-related protein-labeled lipid bodies. The colocalization of COX-2 at lipid bodies was confirmed by immunoblot of subcellular fractionated cells. Direct localization of PGE(2) at its synthesis locale showed that lipid bodies are sources of eicosanoids in the transformed colon cancer cells. Treatment with either aspirin or the fatty acid synthase inhibitor C75 significantly reduced the number of lipid bodies and PGE(2) production in CACO-2 and in IEC-6 H-rasV12 cells with effects in cell proliferation. Together, our results showed that lipid bodies in colon cancer cells are dynamic and functional active organelles centrally involved in PGE(2) synthesis and may potentially have implications in the pathogenesis of adenocarcinoma of colon.
引用
收藏
页码:1732 / 1740
页数:9
相关论文
共 54 条
[21]   ULTRASTRUCTURAL-LOCALIZATION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE (CYCLOOXYGENASE) TO ISOLATED, PURIFIED FRACTIONS OF GUINEA-PIG PERITONEAL MACROPHAGE AND LINE 10 HEPATOCARCINOMA CELL LIPID BODIES [J].
DVORAK, AM ;
WELLER, PF ;
HARVEY, VS ;
MORGAN, ES ;
DVORAK, HF .
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 1993, 101 (02) :136-142
[22]   UP-REGULATION OF CYCLOOXYGENASE-2 GENE-EXPRESSION IN HUMAN COLORECTAL ADENOMAS AND ADENOCARCINOMAS [J].
EBERHART, CE ;
COFFEY, RJ ;
RADHIKA, A ;
GIARDIELLO, FM ;
FERRENBACH, S ;
DUBOIS, RN .
GASTROENTEROLOGY, 1994, 107 (04) :1183-1188
[23]   Caevolin-2 is targeted to lipid droplets, a new "membrane domain" in the cell [J].
Fujimoto, T ;
Kogo, H ;
Ishiguro, K ;
Tauchi, K ;
Nomura, R .
JOURNAL OF CELL BIOLOGY, 2001, 152 (05) :1079-1085
[24]   Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases [J].
Heid, HW ;
Moll, R ;
Schwetlick, I ;
Rackwitz, HR ;
Keenan, TW .
CELL AND TISSUE RESEARCH, 1998, 294 (02) :309-321
[25]   Increased risk of intestinal cancer in Crohn's disease: A meta-analysis of population-based cohort studies [J].
Jess, T ;
Gamborg, M ;
Matzen, P ;
Munkholm, P ;
Sorensen, TIA .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2005, 100 (12) :2724-2729
[26]  
KARGMAN SL, 1995, CANCER RES, V55, P2556
[27]   Fatty acid synthase and cancer: New application of an old pathway [J].
Kuhajda, FP .
CANCER RESEARCH, 2006, 66 (12) :5977-5980
[28]   Synthesis and antitumor activity of an inhibitor of fatty acid synthase [J].
Kuhajda, FP ;
Pizer, ES ;
Li, JN ;
Mani, NS ;
Frehywot, GL ;
Townsend, CA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3450-3454
[29]   Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic [J].
Liu, PS ;
Ying, YS ;
Zhao, YM ;
Mundy, DI ;
Zhu, MF ;
Anderson, RGW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (05) :3787-3792
[30]   The biogenesis and functions of lipid bodies in animals, plants and microorganisms [J].
Murphy, DJ .
PROGRESS IN LIPID RESEARCH, 2001, 40 (05) :325-438