MUC1* mediates the growth of human pluripotent stem cells.
The MUC1 protein is aberrantly expressed on an estimated 75% of all human solid tumor cancers. We recently reported that a transmembrane cleavage product, MUC1*, is the predominant form of the protein on cancer cells [1]. Further, our evidence indicated that MUC1* functions as a growth factor receptor on tumor cells, while the full-length protein appeared to have no growth promoting activity. Here, we report that MUC1* acts as a growth factor receptor on undifferentiated human embryonic stem cells (hESCs). Cleavage of the full-length ectodomain to form MUC1*, a membrane receptor, appears to make binding to its ligand, NM23, possible. Unexpectedly, we found that newly differentiated cells no longer express the cleaved form, MUC1*, or its ligand, NM23. Newly differentiated stem cells exclusively present full-length MUC1. Antibody-induced dimerization of the MUC1* receptor on hESCs stimulated cell growth to a far greater degree than currently used methods that require the addition of exogenous basic fibroblast growth factor (bFGF) as well as factors secreted by fibroblast "feeder cells". Further, MUC1* mediated growth was shown to be independent of growth stimulated by bFGF or the milieu of factors secreted by feeder cells. Stimulating the MUC1* receptor with either the cognate antibody or its ligand NM23 enabled hESC growth in a feeder cell-free system and produced pluripotent colonies that resisted spontaneous differentiation. These findings suggest that this primal growth mechanism could be utilized to propagate large numbers of pluripotent stem cells for therapeutic interventions.
Hikita
Sherry T
ST
Center for Stem Cell Biology and Engineering, University of California Santa Barbara, Santa Barbara, California, USA.
Kosik
Kenneth S
KS
Clegg
Dennis O
DO
Bamdad
Cynthia
C
D002455:Cell Division / Q000502:physiology*; D017077:Culture Media, Conditioned; D006801:Humans; D008024:Ligands; D018396:Mucin-1 / Q000378:metabolism / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology*
D017077:Culture Media, Conditioned; D008024:Ligands; C060192:MUC1 protein, human; D018396:Mucin-1