Knockdown of peroxisome proliferator-activated receptor-beta induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells.
The role of peroxisome proliferator-activated receptor-beta/delta (PPAR-beta/delta) in the pathogenesis of colon cancer remains highly controversial. This study specifically silenced the PPAR-beta expression in three colon cancer cell lines with different metastatic potentials. Although PPAR-beta knockdown resulted in more malignant morphological changes, bigger colony sizes and lower carcinoembryonic antigen (CEA) secretion, and enhanced the cell-fibronectin adhesion, cell invasion and migration were unaffected. These effects were stronger in poorly metastatic cell lines compared with highly metastatic ones. Simultaneously, PPAR-beta knockdown decreased the mRNAs encoding adipocyte differentiation-related protein and liver fatty acid binding protein, and increased the mRNA of ILK, whereas the mRNAs encoding integrin-beta1 and angiopoietin-like 4 were unchanged. Using immunohistochemistry, we determined that the intensity of PPAR-beta expression was stronger in rectal cancers with better differentiation than in those with poor differentiation, and was stronger in early-stage tumors than in advanced ones. Together, these findings consistently indicate that PPAR-beta may facilitate differentiation and inhibit the cell-fibronectin adhesion of colon cancer, having a role as an inhibitor in the carcinogenesis and progression of colorectal cancer. Interestingly, PPAR-beta seems to have a more important role in poorly metastatic cells than in highly metastatic ones.
Yang
L
L
Division of Oncology, Department of Clinical and Experiment Medicine, Linköping University, S-581 85 Linköping, Sweden.
Olsson
B
B
Pfeifer
D
D
Jönsson
J-I
JI
Zhou
Z-G
ZG
Jiang
X
X
Fredriksson
B-A
BA
Zhang
H
H
Sun
X-F
XF
D000368:Aged; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D048430:Cell Shape; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D002272:Carcinoembryonic Antigen; D005353:Fibronectins; D048068:PPAR-beta