Lack of Muc1-regulated beta-catenin stability results in aberrant expansion of CD11b+Gr1+ myeloid-derived suppressor cells from the bone marrow.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that inhibit T-cell activity and contribute to the immune suppression characteristic of most tumors. We discovered that bone marrow (BM) progenitor cells from the Muc1 knockout (KO) mice differentiated into CD11b(+)Gr1(+) MDSCs in vitro under granulocyte macrophage colony-stimulating factor and interleukin-4 signaling. MUC1 is a tumor-associated mucin and its cytoplasmic tail (MUC1-CT) can regulate beta-catenin to promote oncogenesis. Given the importance of beta-catenin in hematopoiesis, we hypothesized that the MUC1 regulation of beta-catenin is important for MDSC development. Our current study shows that the aberrant development of BM progenitors into CD11b(+)Gr1(+) MDSCs is dependent on the down-re

SUBMITTER: Poh TW 

PROVIDER: S-EPMC2705196 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature