Disease relevance of CD97

• Expression of the EGF-TM7 receptor CD97 and its ligand CD55 (DAF) in multiple sclerosis [1].
• CD97, a membrane protein expressed at high levels on inflammatory cells and some carcinomas, is a member of the adhesion G protein-coupled receptor family, whose members have bipartite structures consisting of an extracellular peptide containing adhesion motifs noncovalently coupled to a class B 7-transmembrane domain [2].
• Moreover, more strongly CD97-stained tumor cells at the invasion front of colorectal carcinomas indicate the involvement of the molecule in tumor migration and invasion [3].
• Second, we screened 81 colorectal adenocarcinomas by immunohistology for expression of CD97 [3].
• Expression of the epidermal growth factor seven-transmembrane member CD97 correlates with grading and staging in human oral squamous cell carcinomas [4].

High impact information on CD97

• The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF) [5].
• CD97 is an activation-induced antigen on leukocytes with a seven-span transmembrane (7-TM) region homologous to the secretin receptor superfamily [5].
• By demonstrating that lymphocytes and erythrocytes specifically adhere to CD97-transfected COS cells we here show that CD97 in parallel with its molecular evolution has acquired the ability to bind cellular ligands [5].
• A mAb selected on its capacity to block the adhesion between CD97 transfectants and red cells was found to be directed to the NH2-terminal short consensus repeat (SCR) of decay accelerating factor (DAF, CD55), a regulatory protein of the complement cascade [5].
• However, in contrast to this group of peptide hormone receptors, CD97 has an extended extracellular region with three EGF domains at the NH2 terminus, two of them with a calcium binding site [5].

Chemical compound and disease context of CD97

• The aim of this study was to analyze the expression of the CD97 protein in thyroid carcinomas and the role of all-trans-retinoic acid (RA) in the regulation of CD97 protein in monolayer culture of the human follicular thyroid carcinoma cell line FTC-133 [6].

Biological context of CD97

• Thus, alternative splicing may regulate the ligand specificity of CD97 and probably other members of the EGF-TM7 family [7].
• Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97 [8].
• Transient transfection of human embryonic kidney (HEK) 293 cells with the mouse CD97 cDNA in a green-fluorescence protein vector (pEGFP-N1) showed plasma membrane targeting of the expressed protein [9].
• By comparing EGF-TM7 receptors in primates and dogs, we identified an intriguing pattern of concerted evolution, apparently mediated by gene conversion, among EMR2 and the oppositely orientated and physically adjacent genes CD97 and EMR3 [10].
• SW 1736, HTh 74, and 8505 C cells apparently expressed CD97 with alternative glycosylation compared to peripheral lymphocytes, whereas most of the CD97 antigen presented on thyrocytes and C 643 cells had glycosylation sites resembling those of lymphocytes [11].

Anatomical context of CD97

• Unlike CD97, no expression was observed on resting or activated lymphocytes [12].
• Moreover, the CD97 isoform pattern was not altered in monocytes after interferon-gamma stimulation and in synovial T cells from patients with rheumatoid arthritis [13].
• The interaction between CD97/EMR2 and CS may therefore play a role in the interaction of activated T cells, dendritic cells, and macrophages with B cells [14].
• The contribution of CD97 (EGF 1,2,3,5) and CD97 (EGF 1,2,3,4,5) to total CD97 levels varied among most cell types only slightly, although relatively higher mRNA levels of both isoforms were detected in U 937 cells and monocytes [13].
• Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells [14].

Associations of CD97 with chemical compounds

• CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells [2].
• It was found that coengagement of alpha5beta1 and chondroitotin sulfate proteoglycan by CD97 synergistically initiates endothelial cell invasion [2].
• CD97 is a dimeric glycoprotein of Mr 75,000-85,000 and 28,000 belonging to a novel subfamily of seven-span transmembrane region leukocyte cell surface molecules [11].
• Different from these receptors, CD97 has an extended extracellular region of 433 amino acids that possesses three N-terminal epidermal growth factor-like domains, two of them with a calcium-binding site, and a single Arg-Gly-Asp (RGD) motif [15].
• TSH, forskolin, phorbol 12-myristate 13-acetate, and insulin showed no effect after 72-h pretreatment with RA, whereas epidermal growth factor treatment led to a slight increase in the number of the CD97-positive cells (from 30% to 40%) compared to the control value [6].

Physical interactions of CD97

• Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97 [7].

Regulatory relationships of CD97

• The findings suggest that adhesive activity of CD97 toward CD55 is unlikely to be regulated by differential CD97 isoform expression [13].
• CD97 is a dimeric glycoprotein belonging to the secretin receptor superfamily and is abundantly expressed in cells of hematopoietic origin [6].

Other interactions of CD97

• Use of 2A1 has demonstrated EMR2, like CD97, to be expressed as a heterodimeric receptor consisting of an extracellular alpha part and a TM7/cytoplasmic beta part [12].
• It is interesting that in contrast with CD97 and EMR2, CD34(+)CD33(-)/CD38(-) committed hematopoietic stem cells and CD34(+)CD33(+)/CD38(+) progenitors in bone marrow do not express EMR3 [16].
• Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55) [9].
• The EGF-TM7 family (CD97 and EMR1) is a group of class II seven-span transmembrane receptors predominantly expressed by cells of the immune system [17].
• The EGF domain region of the recently identified EMR2 differs from that of CD97 in only 6 out of 236 amino acids [12].

Analytical, diagnostic and therapeutic context of CD97

• The functional consequences of CD97-CD55 binding are largely unknown, but previous data imply that CD97-CD55 interactions play a role in cellular activation, migration, and adhesion under inflammatory conditions.Here we examined the expression of CD97 and CD55 by immunohistochemistry in multiple sclerosis (MS) [1].
• Molecular cloning and characterization of mouse CD97 [17].
• Furthermore, a sandwich ELISA showed significantly (p<0.05) elevated levels of soluble CD97 in serum but not in cerebrospinal fluid of MS patients (37%) compared to healthy controls (8%).Collectively, these data suggest that CD97-CD55 interactions are involved in the inflammatory processes in MS [1].
• Northern blot analysis revealed that CD97 is expressed widely in mouse tissues and in resting as well as activated cultured mouse splenocytes [9].
• Western blot analysis confirmed its membrane association and identified the existence of a processed C-terminal fragment, supporting the notion that CD97 on the cell membrane is composed of post-translationally generated subunits [9].

References