Disease relevance of SSFA2

• Deregulated expression of KRAP, a novel gene encoding actin-interacting protein, in human colon cancer cells [1].
• Of particular importance are observations demonstrating that CS1-mediated melanoma cell adhesion could be inhibited by interfering with CSPG synthesis or expression [2].
• A conserved residue in the tip proteins of CS1 and CFA/I pili of enterotoxigenic Escherichia coli that is essential for adherence [3].
• The relative abundance of the fibronectin mRNA containing the CS1 sequence was significantly increased in both fetal and cancerous liver tissues, although it was not affected in nonmalignant tissues with chronic hepatitis and cirrhosis [4].
• The four genes essential for CS1 pilus morphogenesis, cooB, A, C and D, are arranged in an operon and encode structural and assembly proteins unlike those of other pilus systems commonly associated with Gram-negative bacteria [5].

High impact information on SSFA2

• Here we report that day-12 colony-forming-unit spleen (CFU-S12)5 cells and reconstituting haematopoietic stem cells attach to the C-terminal, heparin-binding fragment of fibronectin by recognizing the CS-1 peptide of the alternatively spliced non-type III connecting segment (IIICS) of human plasma fibronectin [6].
• Moreover, eosinophil migration over FN-preincubated or HUVEC-covered filters was significantly inhibited by anti-connecting segment 1 (CS-1) mAbs, as well as the soluble CS-1 peptide (unlike migration across bare untreated filters) [7].
• (c) Both primitive LTBMC-IC and clonogenic progenitors adhere to the three known cell-attachment sites in the 33/66 kD cell-adhesion promoting fragment, FN-C/H I, FN-C/H II and CS1 [8].
• Finally, the ability to block adhesion of LTBMC-IC to intact irradiated stroma with peptides FN-C/H II, FN-C/H I and CS1 suggests that receptors responsible for this interaction may be important in the homing of primitive progenitors to the bone marrow [8].
• Furthermore, mAb's specific for CD49d and CD106, or the synthetic CS1 fibronectin peptide, could inhibit B-cell pseudoemperipolesis [9].

Chemical compound and disease context of SSFA2

• Importantly, when melanoma cells were cultured on substrata coated with CS1 and then stimulated with 9.2.27-conjugated microsphere beads, formation of focal contacts and stress fibers was also observed, indicating that NG2 can collaborate with alpha 4 beta 1 integrin when each receptor is engaged on distinct and separate substrata [10].
• When RGDS peptide homologues were tested for their ability to inhibit spreading of melanoma cells on CS1- and CS5-IgG conjugates, GRGDS, GRGES, and REDV were found to be inhibitory, while GRDGS had no effect [11].
• When N-terminal cysteine derivatives of the CS peptides were conjugated to IgG by covalent cross-linking with N-succinimidyl-3(2-pyridyldithio)propionate, both the CS1 and CS5 conjugates promoted B16-F10 melanoma cell spreading [12].
• These results indicate that the C-terminal cell- and heparin-binding domain of fibronectin mediates HL-60 cell binding by direct interaction independently of RGD, CS1, and melanoma cell adhesion domains in this fragment [13].
• These results indicate that CS1 peptide of fibronectin, lacking the Arg-Gly-Asp-containing domain, actively inhibits tumor metastases in spontaneous and experimental metastasis models [14].

Biological context of SSFA2

• The CS-1 cDNA clone was isolated by immunological screening of a human testis lambda gt11 cDNA library with mono-specific polyclonal antibody against CS-1 [15].
• Polyclonal antibodies to CS-1 inhibit the early cleavage of fertilized eggs without apparently affecting sperm penetration and pronuclear formation [15].
• Finally, it was found that recognition of both the RGDS domain and CS1 binding site by neural crest cells involved receptors belonging to the integrin family [16].
• Coordinate oncodevelopmental modulation of alternative splicing of fibronectin pre-messenger RNA at ED-A, ED-B, and CS1 regions in human liver tumors [4].
• New tools in an old trade: CS1 pilus morphogenesis [5].

Anatomical context of SSFA2

• The transcribed CS-1 RNA was translated in a rabbit reticulocyte in vitro translation system and produced a 33-kDa reCS-1 protein, as assessed by migration in a SDS-polyacrylamide gel.(ABSTRACT TRUNCATED AT 250 WORDS)[15]
• In normal tissues, KRAP was strongly expressed in pancreas and testis [1].
• While KRAP was rarely expressed in normal colon epithelium, deregulated constitutive KRAP expression was observed in some other colon cancer cells [1].
• We have identified a novel gene, designated KRAP (Ki- ras-induced actin-interacting protein), encoding a protein of 1,259 amino acids with coiled-coil regions and transmembrane regions, from the cDNA library of human colon cancer HCT116 cells, as one of the genes upregulated by activated Ki- ras [1].
• Anti-KRAP polyclonal antibodies detected endogenous KRAP as the molecular size of Mr 180,000, and immunofluorescence microscopy and cytochalasin E treatment revealed that KRAP was clearly associated with the actin filaments [1].

Associations of SSFA2 with chemical compounds

• Binding was abrogated by both anti-alpha 4 integrin and CS1 peptides [17].
• Both anti-CS-1 and an antibody to activated beta1 showed increased staining on the luminal endothelium of human coronary lesions with active monocyte entry [18].
• Monoclonal antibodies against both the alpha 5 and the beta 1 subunits of the classical fibronectin receptor as well as an Arg-Gly-Asp (RGD) peptide inhibited attachment, whereas anti-alpha 4 monoclonal antibodies and the CS1 peptide did not [19].
• Two nonadjacent CS peptides, designated CS1 and CS5, were inhibitory [12].
• Triiodothyronine treatment of transiently transfected GC cells had little effect on CAT activity from the hGH-1 gene hybrid but increased CAT activity from the hCS-1 gene hybrid [20].

Other interactions of SSFA2

• The CS-1 cDNA was cloned in the transcription vector, pGEM-11Zf, to obtain high-level in vitro transcription by SP6 and T7 RNA polymerase [15].

Analytical, diagnostic and therapeutic context of SSFA2

• The ability of a synthetic peptidomimetic of connecting segment-1 (CS-1 peptide) to block the recruitment of leukocytes and the accumulation of lipid in the aortic sinus of either wild-type mice (strain C57BL/6J) or mice with a low-density lipoprotein null mutation (LDLR-/-) maintained on an atherogenic diet was assessed [21].
• Examination by PCR of 17 other unrelated CS1 ETEC strains with a variety of serotypes demonstrated that all contained at least parts of both replicons of pCoo and that strains of the O6 genotype appear to contain a cointegrate very similar to pCoo [22].
• METHODS--The effect of the synthetic peptide CS1 on lymphocyte binding to human synovial and peripheral lymph node high endothelial venules (HEVs) was measured in an in vitro frozen section assay [23].
• A total of 370 patients (63%) had early clinical stages (CS) of disease; 295 (50%) had CS1, 32 (5%) had CS1Mk+ (CS1 with pathological serum tumor marker patterns after orchiectomy) and 43 (7%) had CS2A disease [24].
• Pathological staging with retroperitoneal lymph node dissection (RPLND) of the retroperitoneum was performed in 345 (93%) of the early CS patients and 128 (37%) had pathological stage 2 (PS2) disease; 27% of the CS1, 100% of the CS1Mk+ and 66% of the CS2A patients [24].

References