ABSTRACT
Natural killer (NK) cells derived or isolated from different sources have been gaining in importance for cancer therapies. In this study, we evaluate and compare key characteristics between NK cells derived or isolated from umbilical cord blood, umbilical cord blood hematopoietic stem/progenitor cells, peripheral blood, and induced pluripotent stem cells (iPSCs). Specifically, we find CD56+ NK cells isolated and expanded directly from umbilical cord blood (UCB56) and NK cells derived from CD34+ hematopoietic stem/progenitors in umbilical cord blood (UCB34) differ in their expression of markers associated with differentiation including CD16, CD2, and killer Ig-like receptors (KIRs). UCB56-NK cells also displayed a more potent cytotoxicity compared to UCB34-NK cells. NK cells derived from iPSCs (iPSC-NK cells) were found to have variable KIR expression, with certain iPSC-NK cell populations expressing high levels of KIRs and others not expressing KIRs. Notably, KIR expression on UCB56 and iPSC-NK cells had limited effect on cytotoxic activity when stimulated by tumor target cells that express high levels of cognate HLA class I, suggesting that in vitro differentiation and expansion may override the KIR-HLA class I mediated inhibition when used across HLA barriers. Together our results give a better understanding of the cell surface receptor, transcriptional, and functional differences between NK cells present in umbilical cord blood and hematopoietic progenitor-derived NK cells which may prove important in selecting the most active NK cell populations for treatment of cancer or other therapies.
Subject(s)
Cell Differentiation/immunology , Fetal Blood/cytology , Hematopoietic Stem Cells/immunology , Induced Pluripotent Stem Cells/cytology , Killer Cells, Natural/immunology , Neuroblastoma/immunology , Receptors, KIR/immunology , Cell Differentiation/genetics , Cell Line, Tumor , Cell Survival/immunology , Genotype , HLA Antigens/genetics , HLA Antigens/immunology , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/immunology , Humans , Neuroblastoma/pathology , Receptors, KIR/genetics , TransfectionABSTRACT
Sulforaphane (SF) exhibits an anti-tumor effect in a variety of cancers, but little is known about its function in nasopharyngeal carcinoma. SF could decrease the expression of stem cell markers, ß-catenin, Nanog, c-Myc, Oct3/4 and Sox2 in nasopharyngeal cancer cells (HONE1 and SUN1), and inhibit the formation of tumor spheres. Moreover, SF inhibits proliferation and induces apoptosis decreasing the stemness of nasopharyngeal cancer cells through a mechanism related to STAT3 signaling in vitro. We found that SF inhibits total STAT3 expression level and STAT3 phosphorylation (troy 704 and troy 705) by upregulation of miRNA-124-3p. Our results provide the evidence for discovering the novel drugs against nasopharyngeal carcinoma, and potential drugs targeting STAT3 signaling pathway.