AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.
BACKGROUND
Radiotherapy is a well-established anti-cancer treatment. Although radiotherapy has been shown to significantly decrease the local relapse in rectal cancer patients, the rate of distant metastasis is still very high. The aim of this study was to evaluate whether AEG-1 is involved in radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.


RESULTS
Migration and invasion were decreased in all the AEG-1 knockdown cell lines. Furthermore, we observed that radiation enhanced migration and invasion, while AEG-1 knockdown abolished this effect. The results from the zebrafish embryo model confirmed the results obtained in vitro. MMP-9 secretion and expression were decreased in AEG-1 knockdown cells.


METHODS
We evaluated the involvement of AEG-1 in migration and invasion and, radiation-enhanced migration and invasion by Boyden chamber assay in three colon cancer cell lines and respective stable AEG-1 knockdown cell lines. Furthermore, we injected those cells into zebrafish embryos and evaluated the amount of disseminated cells into the tail.


CONCLUSIONS
AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced invasion both in vitro and in vivo. We speculate that this is done via the downregulation of the intrinsic or radiation-enhanced MMP-9 expression by AEG-1 in the cancer cells. This study also shows, for the first time, that the zebrafish is a great model to study the early events in radiation-enhanced invasion.
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Sebastian
S
Gnosa
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Alessandra
A
Capodanno
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Raghavendra Vasudeva
RV
Murthy
Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Lasse Dahl Ejby
LD
Jensen
Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Xiao-Feng
XF
Sun
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D016601:RNA-Binding Proteins; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000528:radiation effects; D014162:Transfection; D015027:Zebrafish / Q000196:embryology
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
MTDH; colon cancer; radiation; transwell migration and invasion; zebrafish