Human mesenchymal stem cell transformation is associated with a mesenchymal-epithelial transition.
Carcinomas are widely thought to derive from epithelial cells with malignant progression often associated with an epithelial-mesenchymal transition (EMT). We have characterized tumors generated by spontaneously transformed human mesenchymal cells (TMC) previously obtained in our laboratory. Immunohistopathological analyses identified these tumors as poorly differentiated carcinomas, suggesting that a mesenchymal-epithelial transition (MET) was involved in the generation of TMC. This was corroborated by microarray and protein expression analysis that showed that almost all mesenchymal-related genes were severely repressed in these TMC. Interestingly, TMC also expressed embryonic antigens and were able to integrate into developing blastocysts with no signs of tumor formation, suggesting a dedifferentiation process was associated with the mesenchymal stem cell (MSC) transformation. These findings support the hypothesis that some carcinomas are derived from mesenchymal rather than from epithelial precursors.
Rubio
Daniel
D
Centro de Biología Molecular Severo Ochoa, Nicolás Cabrera 1, UAM Campus de Cantoblanco, E-28049 Madrid, Spain.
Garcia
Silvia
S
De la Cueva
Teresa
T
Paz
Ma F
MF
Lloyd
Alison C
AC
Bernad
Antonio
A
Garcia-Castro
Javier
J
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D054337:Cell Dedifferentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000648:ultrastructure; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D012333:RNA, Messenger; D014746:Vimentin; D007633:Keratins