ABSTRACT
This study was aimed to explore the difference of NK cell receptor NKG2D and NKG2A expression on NK cells and CD3(+) T cells and their ligand MHC-I A/B (major histocompatibility complex class I-related chains A/B) and HLA-E expression in leukemia cells, as well as its immunological significance. Flow cytometry was used to detect the killing rate of NK92 cells to 8 leukemia cell lines, and the expression of NKG2D and NKG2A on NK cells and CD3(+) T cells as well as their ligand MHC-I A/B and HLA-E expression on leukemia cells. The results indicated that the NK92 showed different killing activity to different leukemia cell lines. The positive expression rate of NKG2D and NKG2A on NK cells and CD3(+) T cells in ALL patients was no significantly different from that in AML patients (p > 0.05), but positive expression rate of MHC-I A/B and HLA-E in ALL patients was obviously higher than that in AML patients (p < 0.05). It is concluded that there is difference of immune cell function between ALL and AML patients, this difference may be associated with the expression difference of NKG2D and NKG2A ligands on leukemia cells while does not associated with the killing and inhibiting receptors expressed on NK cells and CD3(+) T cells.
Subject(s)
Histocompatibility Antigens Class I/metabolism , Leukemia, Myeloid, Acute/genetics , NK Cell Lectin-Like Receptor Subfamily C/metabolism , NK Cell Lectin-Like Receptor Subfamily K/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Histocompatibility Antigens Class I/genetics , Humans , Infant , Leukemia, Myeloid, Acute/metabolism , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily C/genetics , NK Cell Lectin-Like Receptor Subfamily K/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Young Adult , HLA-E AntigensABSTRACT
Receptor protein tyrosine kinases (RPTKs) play important roles in the regulation of a variety of cellular processes including cell migration, proliferation, and protection from apoptosis. Here, we report the identification and characterization of a novel RPTK-like molecule that has a critical role in induction of tumorigenesis and metastasis and is termed Novel Oncogene with Kinase-domain (NOK). NOK contains a putative single transmembrane domain and a conserved intracellular tyrosine kinase domain that shares homology with members of the platelet-derived growth factor/fibroblast growth factor receptor superfamily. NOK was exclusively located in the cytoplasm. NOK mRNAs were detected in limited human organs and expressed with the highest abundance in the prostate. A variety of tumor cells also expressed the NOK mRNAs. We demonstrated that NIH3T3 and BaF3 cells could be strongly transformed by the expression of the NOK gene as examined by colony formation experiment. In addition, BaF3 cells with the stable expression of NOK induced rapid tumorigenesis in nude mice. Interestingly, these NOK-expressing tumor cells could promptly invade and spread into various distinct organs and form metastatic foci, eventually leading to the rapid death of these animals. Moreover, molecular mechanism studies indicated that NOK could concomitantly activate both MAP kinase and phosphatidylinositol 3'-kinases (PI3K) pathways in stable BaF3 cells. Thus, our results both in vitro and in vivo suggest that NOK is a novel oncogene with the capacity of promoting cell transformation, tumorigenesis, and metastasis.
Subject(s)
Cell Transformation, Neoplastic/genetics , Oncogene Proteins/genetics , Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Fibroblast Growth Factor/genetics , Receptors, Platelet-Derived Growth Factor/genetics , Amino Acid Sequence , Animals , COS Cells , Cell Division/genetics , Cell Line, Tumor , Chlorocebus aethiops , Cloning, Molecular , Humans , MAP Kinase Signaling System/genetics , Mice , Mice, Nude , Molecular Sequence Data , NIH 3T3 Cells , Neoplasm Invasiveness , Oncogene Proteins/physiology , Phosphatidylinositol 3-Kinases/metabolism , Promoter Regions, Genetic , Protein-Tyrosine Kinases/physiology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptor Protein-Tyrosine Kinases/physiology , Sequence Homology, Amino Acid , TransfectionABSTRACT
Anomers of monovalent and divalent beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy-D-gluco-pyranosides were synthesized under different glycosylation conditions, and evaluated for in vitro antimetastatic activity. Three compounds showed promising inhibitory effects on cancer cell attachment, spreading, migration, and invasion.
