Disease relevance of CD164

• Functional studies demonstrated that blocking CD164 on prostate cancer cell lines reduced the ability of these cells to adhere to human bone marrow endothelial cells, and invade into extracellular matrices [1].
• MGC-24 mRNA was intensely expressed in normal tissues of the colon, small intestine and thyroid, and in some nude mouse-transplanted colorectal and pancreatic adenocarcinomas [2].
• The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis [1].
• The total MGC-24 RNA level was found to be lower in human colorectal carcinomas as compared with the adjacent normal mucosal tissues [3].
• Lower MGC-24 mRNA levels in colon carcinomas and in the adjacent normal mucosa epithelium correlate with lymphatic vessel invasion by the carcinoma [3].

High impact information on CD164

• They were also positive for CD164 and CD172a (signal regulatory protein-alpha) and for a stem cell antigen defined by the recently described antibody W7C5 [4].
• In this article, we demonstrate that these 2 CD164 epitopes are expressed on CD34(+) cells throughout ontogeny, in particular on CD34(+ )cell clusters associated with the ventral floor of the dorsal aorta in the developing embryo and on CD34(+) hematopoietic precursor cells in fetal liver, cord blood, and adult bone marrow [5].
• While higher levels of expression of these CD164 epitopes occur on the more primitive AC133(hi)CD34(hi)CD38(lo/-) cell population, they also occur on most cord blood Lin(-)CD34(lo/-)CD38(lo/- )cells, which are potential precursors for the AC133(hi)CD34(hi)CD38(lo/-) subset [5].
• This is particularly striking in the colon, where infiltrating lymphoid cells are CD164 class I-positive but class II-negative, while epithelia are weakly CD164 class II-positive [5].
• The sialomucin CD164 (MGC-24v) is an adhesive glycoprotein expressed by human hematopoietic progenitors and bone marrow stromal cells that serves as a potent negative regulator of hematopoiesis [6].

Biological context of CD164

• Here, we document five new CD164 mAbs, the 96 series, that rely on conformational integrity, but not glycosylation, of exons 2- and 3-encoded CD164 domains, thereby resembling the class III mAbs, N6B6 and 67D2 [7].
• Endolyn (CD164) is a sialomucin that functions as an adhesion molecule and a negative regulator of CD34+ CD38- human haematopoietic precursor cell proliferation [7].
• We have extended these studies further by identifying Pl artificial chromosome (PAC) clones containing the CD164 gene and have used these to localize the CD164 gene specifically to human chromosome 6q21 [8].
• Whereas the human CD164 gene is located on chromosome 6q21, the mouse gene occurs in a syntenic region on chromosome 10B1-B2 [9].
• Collectively, this study indicates that the previously observed differential expression of CD164 epitopes in adult tissues is linked with cell type specific post-translational modifications and suggests a role for epitope-associated carbohydrate structures in CD164 function [10].

Anatomical context of CD164

• Flow cytometric analyses revealed that, on average, 63% to 82% of human bone marrow and 55% to 93% of cord blood CD34(+) cells are CD164(+), with expression of the 105A5 epitope being more variable than that of the other identified epitopes [8].
• Functional studies demonstrate a role for CD164 in the adhesion of hematopoietic progenitor cells to BM stromal cells in vitro [6].
• This molecule was clustered as CD164 at the recent workshop on human leukocyte differentiation antigens [6].
• Both antibodies detected CD164/MGC-24v protein expression by BM stroma and subpopulations of the CD34(+) cells, which include the majority of clonogenic myeloid (colony-forming unit-granulocyte-macrophage [CFU-GM]) and erythroid (blast-forming unit-erythroid [BFU-E]) progenitors and the hierarchically more primitive precursors (pre-CFU) [6].
• CD164 monoclonal antibodies that block hemopoietic progenitor cell adhesion and proliferation interact with the first mucin domain of the CD164 receptor [10].

Associations of CD164 with chemical compounds

• Transmembrane glycoprotein sialomucins, including CD34 and CD164, have been implicated in cell-to-cell interactions and activation [11].
• High levels of sialylation in alpha2-3 and alpha2-6 linkages, without sialyl-Lewis X, indicate that the majority of these hCD164 recombinant proteins are unable to bind to selectins in our assay system, but may interact with Siglec molecules [7].
• The other core protein was a novel one called MGC-24, which has a molecular mass of 24 kDa, is rich in hydroxyl amino acids and cysteine, and lacks repeating motifs [2].
• Like these and other known lysosomal membrane proteins, endolyn contains a YXXO motif at the C-terminus of its cytoplasmic tail (where O is a bulky hydrophobic amino acid), but with no preceding glycine [12].
• The predicted transmembrane and cytoplasmic tail domains of endolyn, as well as parts of its luminal domain, also show some similarities with lamp-1 and lamp-2 [12].

Regulatory relationships of CD164

• RESULTS: Using prostate cancer cell lines, it was demonstrated that CXCL12 induced both the expression of CD164 mRNA and protein [1].

Other interactions of CD164

• Additional phenotyping of these cells using CD117, Thy-1, CD164 and CD133 demonstrated variable primitive status detectable within the external CD34- population [13].
• By confocal microscopy, human CD164 in CD34(+)CD38(+) hematopoietic progenitor (KG1B) and epithelial cell lines appears to be localized primarily in endosomes and lysosomes, with low concentrations at the cell surface [9].
• On the basis of their sensitivities to reducing agents and to sialidase, O-sialoglycoprotease, and N-glycanase treatments, we have characterized CD164 epitopes and grouped them into three classes by analogy with CD34 epitope classification [10].
• While screening prostate cancers for CXCL12-responsive adhesion molecules, we identified CD164 (MGC-24) as a potential regulator of homing [1].
• Among them were signal sequences of CD6, beta2-microglobulin, MGC-24, and T cell receptor epsilon-chain, and at least four novel potential signal sequences [14].
• On presentation of CXCL12 on fibronectin, CD164 associates with CXCR4, an interaction that temporally follows the association of CXCR4 with the integrins VLA-4 and VLA-5 [15].

Analytical, diagnostic and therapeutic context of CD164

• We report here the precise epitope mapping of these mAbs together with that of two other CD164 mAbs, N6B6 and 67D2 [10].
• The dual nature of the CD34 and CD164 antigens discovered here lends further evidence to the previous literature implicating a strong functional link between these two sialomucins, which should be considered in the transplantation arena and in the function of such sialomucins as negative regulators of cell proliferation [11].
• Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of ige-dependent upregulation [16].

References