Decreased synthesis of matrix metalloproteinase-7 and adhesion to the extracellular matrix proteins of human colon cancer cells treated with troglitazone.
OBJECTIVE
In the present study, we investigated the effect of troglitazone, a selective ligand and agonist of PPAR-gamma, on the metastatic potential of human colon cancer cells.


METHODS
High- and low-PPAR-gamma expression clones of the colon cancer cell line, HT29, namely clones 21 and 3 respectively, were used. We investigated the effect of troglitazone on the proliferation, on the adhesion to extracellular matrix proteins and on the synthesis of matrix metalloproteinases (MMPs) of colon cancer cells.


RESULTS
Troglitazone inhibited the proliferation of both subclones, in a dose-dependent manner, and the inhibitory effect correlated with the level of PPAR-gamma expression. Troglitazone strongly inhibited the production of MMP-7, an enzyme associated with invasiveness of cancer cells, by both subclones. In addition, troglitazone caused a strong decrease in the adhesion of clone 21 to extracellular matrix (ECM) proteins, laminin and type IV collagen. This effect was independent of beta1-integrins expression


CONCLUSIONS
In addition to inhibition of cancer cell growth, troglitazone had an inhibitory effect on two important events associated with the metastatic potential of cancer cells, production of MMPs and adhesion to ECM proteins. Consequently, troglitazone is a promising agent for the treatment and prevention of colon cancer metastasis.
Sunami
Eiji
E
Department of Surgical Oncology, Graduate School of Medical Sciences, Faculty of Medicine, University of Tokyo, Japan.
Tsuno
Nelson Hirokazu
NH
Kitayama
Joji
J
Saito
Shinsuke
S
Osada
Takuya
T
Yamaguchi
Hironori
H
Tomozawa
Shigeru
S
Tsuruo
Takashi
T
Shibata
Yoichi
Y
Nagawa
Hirokazu
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D024042:Collagen Type I / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000502:physiology; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism; D000077288:Troglitazone; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002839:Chromans; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D020783:Matrix Metalloproteinase 7; D000077288:Troglitazone