Disease relevance of CD9

• Furthermore, ectopic expression of CD9 in fibrosarcoma cells affected adhesion-induced tyrosine phosphorylation of FAK, that correlated with the reorganization of the cortical actin cytoskeleton [1].
• Anti-CD9 monoclonal antibodies were found to specifically inhibit the transendothelial migration of melanoma cells; the inhibitory effect was likely caused by a strengthening of CD9-mediated heterotypic interactions of TCs to the EC monolayer [2].
• Coprecipitation of CD36, CD9, and alpha6beta1 was also observed on platelets from a patient with Glanzmann thrombasthenia, indicating that alphaII(b)beta3 is not required for the other proteins to associate [3].
• These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis [4].
• Our results indicate that several members of the neuroglandular antigen are expressed in melanoma and that low expression of CD9 on primary melanomas might have prognostic significance with respect to the potential for metastasis [5].

Psychiatry related information on CD9

• In a study of patients attending STD clinics in India, screening for p24 antigen in HIV antibody-negative persons was found to be a reliable and effective research method for determining recent risk behavior and identifying clinical signs of acute primary HIV infection [6].
• Therefore, p24 antigen can be a useful marker for dementia related to HIV-1 infection [7].
• We prospectively evaluated 94 patients with AIDS-dementia complex (ADC) and a smaller group of 27 patients with other HIV-1 related neurological conditions to determine the usefulness of cerebrospinal fluid (CSF) p24 antigen and HIV-1 culture in the diagnosis of ADC [8].
• Quantification of human immunodeficiency virus type 1 p24 antigen and antibody rivals human immunodeficiency virus type 1 RNA and CD4+ enumeration for prognosis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group [9].
• After moderate alcohol consumption there was increased human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells during 28 days of culture without mitogen stimulation as indicated by overnight syncytium formation with SUP-T1 indicator cells and by increased levels of HIV p24 antigen in the culture supernates [10].

High impact information on CD9

• The dose of chemoattractants required to induce motility-related functions is generally at least ten-fold smaller than the dose required to initiate secretory and respiratory burst activities [11].
• COPI-coated vesicle budding from lipid bilayers whose composition resembles mammalian Golgi membranes requires coatomer, ARF, GTP, and cytoplasmic tails of putative cargo receptors (p24 family proteins) or membrane cargo proteins (containing the KKXX retrieval signal) emanating from the bilayer surface [12].
• Patients who received L-697,661 had rapid, dose-related decreases in plasma p24 antigen levels [13].
• Of eight cord-blood samples from neonates with proved HIV infection, five were positive for immune-complex-dissociated p24 antigen [14].
• Early therapy increased the time until CD4+ counts fell below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more conversions from positive to negative for serum p24 antigen [15].

Chemical compound and disease context of CD9

• Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer [16].
• Recently we reported that CD9 is involved in the invasion of a trophoblast-like choriocarcinoma cell line, BeWo, probably through the regulation of integrin functions [17].
• Using Western blot, RT-PCR and immunohistochemistry the expression of CD-9 was analysed in LNCaP cells stimulated during increasing time by the synthetic androgen R1881 and also in 88 specimens of human prostate cancer tissues [18].
• CD9 is a tetra-membrane-spanning glycoprotein involved in cell adhesion, migration, growth signaling and tumor cell metastasis [19].
• RESULTS: Productive HIV-1 infection of intestinal macrophages was demonstrated by the release of p24 antigen, the presence of proviral DNA, and zidovudine inhibition of infection [20].

Biological context of CD9

• Here we show that the appearance of TM4SF protein, CD9, and the formation of CD9-beta1 integrin complexes were both regulated in coordination with murine C2C12 myoblast cell differentiation [21].
• CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor [22].
• Altogether these data show a precise regulation of CD9 during hematopoiesis and suggest a role for this molecule in megakaryocytic differentiation, possibly by participation in membrane remodeling [23].
• CD9 is therefore essential for the IL-16-mediated chemotaxis and activation of the HMC-1 cell line [24].
• Together, these observations demonstrate the presence of a CD38 and HLA-DR signaling complex within tetraspanin-containing lipid rafts and the functional impact of their molecular partner CD9 in antigen presentation [25].

Anatomical context of CD9

• Moreover, PSG17 binding to macrophages from CD9-deficient mice was significantly reduced [26].
• Ectopic expression of CD9 caused a four- to eightfold increase in RD cell syncytia formation, whereas anti-CD9 and anti-CD81 antibodies markedly delayed RD syncytia formation [21].
• In summary, TM4SF proteins such as CD9 and CD81 appear to promote muscle cell fusion and support myotube maintenance [21].
• Finally, anti-CD9 and anti-CD81 monoclonal antibodies triggered apoptotic degeneration of C2C12 cell myotubes after they were formed [21].
• Others, such as CD9 and CD81, remain diffusely distributed at the cell surface.In conclusion, we show that CD151 is a major component of (pre)-hemidesmosomal structures and that its recruitment into hemidesmosomes is regulated by the integrin alpha6beta4 [27].

Associations of CD9 with chemical compounds

• On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system [22].
• Only CD9 is coprecipitated with CD36 from platelets that were solubilized in Brij 96 [3].
• Second, CD9 and alpha(3) integrin colocalized with ganglioside GM1 as seen by double staining of fixed cells [28].
• This association is detected as early as 15 min after metabolic labeling, and the use of Brefeldin A demonstrates that it does not require Golgi modifications of either CD9 or integrin beta1 [29].
• The association of CD63 with CD9 and alphaIIbbeta3, was not inhibited by preincubation of platelets with RGDS or EGTA [30].
• Treatment of CD9-nonexpressing 5T33MMvt cells with the clinically relevant histone deacetylase inhibitor LBH589 resulted in a significant increase in CD9 expression [31].

Physical interactions of CD9

• MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human monocytes [25].
• In support of this conclusion, IL-16 bound to CD9-expressing CHO cell transfectants [24].
• These data indicate that colligin/Hsp47 is anchored to the cell membrane in a complex with CD9 where it moderates tumor cell invasion and motility possibly by acting as a serpin protein inhibitor or as a receptor for collagen [32].
• Finally we demonstrated that epithelial cell adhesion molecule and CD9 form a new primary complex in the tetraspanin web [33].
• We now demonstrate that transmembrane TGF-alpha physically interacts with CD9, a protein with four membrane spanning domains that is frequently coexpressed with TGF-alpha in carcinomas [34].

Co-localisations of CD9

• The CD9 was colocalized with RA-A47 on the cell surface, where it may have affected integrin signaling [35].

Regulatory relationships of CD9

• Anti-CD9 mAbs also inhibited the IL-16-mediated activation of nontransformed human cord blood-derived MCs and mouse bone marrow-derived MCs by 50% to 60% [24].
• Plasma cells showed re-expressed CD9 and downregulated CD37 [36].
• CD9 was expressed on the plasma membrane of enterocytes in crypts and at the bases of the villi whereas CD63 demonstrated a unique granular appearance concentrated in the apical cytoplasm below the brush border [37].
• Human and monkey CD9 upregulates DT binding activity of DTR, while mouse CD9 has no upregulation activity [38].
• CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin [39].

Other interactions of CD9

• Co-immunoprecipitation of DRAP27/CD9 with DTR and chemical cross-linking suggest a tight association of these membrane-bound proteins [40].
• However, circulating TdT+ cells infrequently expressed CD19 (4.5%) and CD9 (2.3%), compared with their marrow counterparts (74% and 47%, respectively) [41].
• CD34(high)CD38(low)Thy1(+) primitive progenitors are contained in the population with intermediate CD9 expression, thus suggesting that CD9 expression may precede CD38 appearance [23].
• CD36 associates with CD9 and integrins on human blood platelets [3].
• Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1 [22].

Analytical, diagnostic and therapeutic context of CD9

• We confirmed binding of PSG17 to CD9 by ELISA, flow cytometry, alkaline phosphatase binding assays, and in situ rosetting [26].
• Dynamic studies by time-lapse immunofluorescence confocal microscopy showed an active redistribution of endothelial CD9 to points of melanoma insertion [2].
• Antibody ligation of cell surface CD9 increased the number of human CFU-MK progenitors and reduced the production of CD41(+) megakaryocytic cells in liquid culture [23].
• Reciprocal immunoprecipitations with antibodies to CD9, alpha6, alphaIIb, or beta3 from Brij 99-solubilized platelets coprecipitated CD36 [3].
• Indeed, we established CD9, CD81 and CD82 promoter methylation in MM cell lines employing methyl-specific-PCR of bisulfite modified G-DNA and PCR of G-DNA digested with methylation-sensitive restriction enzyme (Hin6I) [42].

References