Secretome-based proteomic profiling of Ras-transformed MDCK cells reveals extracellular modulators of epithelial-mesenchymal transition.
Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenetic process by which epithelial cells lose their basic morphological characteristics such as cell-cell contact and gain mesenchymal properties such as increased motility and invasiveness. To gain insights into proteins released from cells that modulate the EMT process, we compared secretome protein expression profiles of MDCK cells and Ras-transformed MDCK cells (21D1) that stably express oncogenic Ras using 2D-DIGE/LC-MS/MS. Differentially expressed secretome proteins were compared with their corresponding gene expression profiles using the Affymetrix GeneChip system. Down-regulated proteins were predominantly involved with cell-cell contact and cell-matrix adhesion (e.g., desmocollin 2, clusterin, collagen XVII and transforming growth factor-beta induced protein ig-h3), while up-regulated proteins were proteases and factors that promote migration (MMP-1, kallikrein 6, TIMP-1, and S100A4/metastasin). Many of the secretome proteins identified in this study have not been previously identified in the context of EMT and may shed light on the underlying mechanisms associated with this cellular process.
Mathias
Rommel A
RA
Joint Proteomics Laboratory, Ludwig Institute for Cancer Research and the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Wang
Bo
B
Ji
Hong
H
Kapp
Eugene A
EA
Moritz
Robert L
RL
Zhu
Hong-Jian
HJ
Simpson
Richard J
RJ
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002853:Chromatography, Liquid; D004285:Dogs; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D055571:Secretory Pathway; D053719:Tandem Mass Spectrometry; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D020543:Proteome; D018631:ras Proteins