Conjugated linoleic acid (CLA) modulates prostaglandin E2 (PGE2) signaling in canine mammary cells.
BACKGROUND
Conjugated linoleic acid (CLA), a naturally occurring linoleic acid isomer found in ruminant-produced foods, has the potential to serve as an effective chemopreventive nutriceutical factor for breast cancer prevention based upon previous published studies. There are several CLA isomers in ruminant-produced food products, among which t10,c12-CLA and c9,t11-CLA are more potent. Expression of cyclooxygenase 2 (COX-2) in mammary tumors has been correlated with poor prognosis. Prostaglandin E2 (PGE2) is a major COX-2 product in various cancers and, as in humans, PGE2 concentrations in canine tumor tissues were frequently elevated. Moreover, a PGE2 receptor subtype, EP2, is highly expressed in mammary tumors. Thus, various studies have implicated the important role of PGE2 and EP2 in COX-2-regulated tumor development.


METHODS
Mammary tumor and normal mammary tissues were both collected from a female dog with mammary tumor. Both malignant and normal mammary tissues were subjected to isolation of epithelial and stromal cells. The effects of t10,c12-CLA and c9,t11-CLA on proliferation, as well as COX-2 and EP2 protein expression in canine mammary normal and cancerous cells, were detected by CellTiter 96 AQueous assay and Western blot assay, respectively.


RESULTS
Both t10,c12-CLA and c9,t11-CLA not only suppressed malignant mammary cell growth, but also exerted inhibitory effects on tumor-associated non-malignant mammary cells. Similarly, both t10,c12-CLA and c9,t11-CLA suppressed EP2 protein expression in both normal and malignant mammary cells. t10,c12-CLA was more effective in decreasing COX-2 protein expression in malignant mammary cells, while, in contrast, c9,t11-CLA down-regulated COX-2 protein expression in both normal and malignant mammary cells.


CONCLUSIONS
The results indicate that the dietary component CLA regulates COX-2 and EP2 protein expression in both malignant mammary cells and cells from the tumor-associated stromal compartment. In turn, this may suppress PGE2 signaling, leading to better prognosis. We further speculate that the knowledge obtained from canine studies may also be beneficial to study human breast cancer.
Wang
Li-Shu
LS
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Huang
Yi-Wen
YW
Liu
Suling
S
Chang
Hsiang-Lin
HL
Ye
Weiping
W
Shu
Sherry
S
Sugimoto
Yasuro
Y
Funk
Julie A
JA
Smeaks
Daniel D
DD
Hill
Lawrence N
LN
Lin
Young C
YC
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D058307:Receptors, Prostaglandin E, EP2 Subtype; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D044243:Linoleic Acids, Conjugated; C545644:PTGER2 protein, human; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; D051546:Cyclooxygenase 2; D015232:Dinoprostone