Conjugated Linoleic Acid Alters Matrix Metalloproteinases of Metastatic Mouse Mammary Tumor Cells

• Published in: The Journal of nutrition Vol. 137; no. 6; pp. 1423 - 1429
• Main Authors: Hubbard, Neil E, Lim, Debora, Erickson, Kent L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.06.2007; American Society for Nutritional Sciences
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; cell lines; conjugated linoleic acid; Diet; disease prevention; enzyme activity; enzyme inhibition; enzyme inhibitors; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; gene expression; in vitro studies; in vivo studies; Linoleic Acids, Conjugated - pharmacology; Linoleic Acids, Conjugated - therapeutic use; mammary glands; mammary neoplasms (animal); Mammary Neoplasms, Animal - enzymology; Mammary Neoplasms, Animal - pathology; Mammary Neoplasms, Animal - prevention & control; messenger RNA; Metalloproteases - antagonists & inhibitors; Metalloproteases - metabolism; metalloproteinases; metastasis; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; protein synthesis; Tissue Inhibitor of Metalloproteinase-1 - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - therapeutic use; Tissue Inhibitor of Metalloproteinase-2 - pharmacology; Tissue Inhibitor of Metalloproteinase-2 - therapeutic use; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Conjugated linoleic acid; Vertebrata; Mammalia; Nutrition; Mouse; Animal; Rodentia; Malignant tumor; Metastasis; Tumor cell
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/137.6.1423

Conjugated linoleic acid (CLA) is a group of linoleic acid derivatives that has been implicated in animal studies to reduce a number of components of mammary tumorigenesis. Previously, we showed that CLA could alter the latency and metastasis of the highly metastatic transplantable line 4526 mouse mammary tumor. Several possible mechanisms have been proposed for the actions of CLA, but here we assessed how CLA may act to alter the expression and activity of matrix-modifying proteins within tumors from line 4526. In vitro, highly metastatic mouse mammary tumor cells had significantly decreased invasiveness after treatment with CLA, an indication that matrix-modifying proteins may have been altered. Using these same highly metastatic cells, primary tumors were grown in mice of separate groups fed 0, 0.1, 0.5, and 1% CLA (wt:wt) and evaluated for their levels and activities of matrix-modifying enzymes, enzyme inhibitors, and enzyme activators. The addition of CLA to the diet increased steady-state levels of messenger RNA (mRNA) of the matrix metalloproteinases (MMP) -2 and -9 in primary tumors removed from mice. However, western analysis revealed that although relative levels of the proform of MMP-9 were consistent with the mRNA observations, MMP-2 proform levels were actually decreased by dietary CLA. The activity of MMP-2 was barely detectable, but gelatin zymography and an in vitro activity assay showed that MMP-9 activity was significantly decreased by CLA. The steady-state mRNA and protein levels of tissue inhibitors of metalloproteinase-1 (TIMP-1) and TIMP-2, natural inhibitors of MMP, were increased at higher dietary CLA levels relative to low or no CLA. Suppression of MMP activity, therefore, may be 1 pathway through which CLA reduces tumor invasion and spread.