Disease relevance of CXCL14

• The majority of head and neck squamous cell carcinoma (HNSCC) and some cervical squamous cell carcinoma do not express CXCL14 mRNA, as opposed to constitutive expression by normal oral squamous epithelium [1].
• CXCL14 mRNA was significantly upregulated in localized prostate cancer and positively correlated with Gleason score [2].
• Antisera against CXCL14 or pertussis toxin blocked this chemotactic effect [3].
• The CXCL14 and CXCL12 chemokines overexpressed in tumor myoepithelial cells and myofibroblasts, respectively, bind to receptors on epithelial cells and enhance their proliferation, migration, and invasion [4].
• In these studies, we report on the nature and specificity of the human anti-murine antibody (HAMA) response in patients given single and multiple infusions of the two Vinca alkaloid conjugates of the MoAb KS1/4, which recognizes tumor-associated antigens in a variety of adenocarcinomas [5].

Psychiatry related information on CXCL14

• The brief version of the MAC-R (the BMAC) and subscale scores correlated significantly with scores from related measures of eating disorders, showing evidence of concurrent validity [6].
• Other aspects, such as the volume of each of the reactants, the pH and the reaction times, were also standardized to yield a labeled IgG2a (KS1/4) that could be consistently tested for biodistribution and tumor-binding [7].

High impact information on CXCL14

• Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation [8].
• Our model assigns unprecedented roles to CXCL14 and epidermal tissue as attractant and niche of differentiation, respectively, in the renewal of Langerhans cells under steady-state conditions [8].
• At the amino acid sequence level, GA733-2 was found to be greater than 99% identical to the previously described KSA antigen defined by monoclonal antibody KS1/4 [9].
• Murine CXCL14 is dispensable for dendritic cell function and localization within peripheral tissues [10].
• We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14(-)(/)(-)) and control mice [10].

Chemical compound and disease context of CXCL14

• Carboxypeptidase A (CP-A) and monoclonal antibody KS1/4 directed against an antigen on human lung adenocarcinoma cells (UCLA-P3) were derivatized by treatment with succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate and N-succinimidyl 3-(2-pyridyldithio)propionate, respectively [11].

Biological context of CXCL14

• Furthermore, evaluating the biologic effect of CXCL14 on DC, we demonstrated that the addition of recombinant human CXCL14 to DC cultures resulted in up-regulation of the expression of DC maturation markers, as well as enhanced proliferation of allogeneic T cells in MLR [1].
• CXCL14 gene expression is altered in a number of cancers, but protein expression levels have not been investigated [12].
• CXCL14 also stimulated the chemotaxis of immature monocyte-derived dendritic cells [3].
• In addition, the downregulation of the expression of CXCL14 might be an important step in successful oncogenesis to prevent NK immune surveillance of the malignancy [3].
• Biosynthesis and glycosylation of the carcinoma-associated antigen recognized by monoclonal antibody KS1/4 [13].

Anatomical context of CXCL14

• BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells [14].
• BRAK/CXCL14 is a CXC chemokine constitutively expressed at the mRNA level in certain normal tissues but absent from many established tumor cell lines and human cancers [14].
• Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality [10].
• Transduction of CXCL14-negative HNSCC cell lines with the human CXCL14 gene resulted in stimulation of DC attraction in vitro and increased tumor infiltration by DC in vivo in chimeric animal models [1].
• Here we report that CXCL14 protein can be expressed in primary epithelial cells; however, in several immortalized and cancer cell lines this protein is targeted for polyubiquitylation and proteasomal degradation [12].

Associations of CXCL14 with chemical compounds

• Furthermore, BRAK expression was demonstrated in B cells and monocytes, after stimulation of peripheral blood mononuclear cells with lipopolysaccharide [15].
• CONCLUSIONS: These results demonstrate that the epimerising activity associated with module 1 of the erythromycin PKS can be conferred on module 5 merely by transfer of the KS1 domain [16].
• The latter was of opposite configuration at three out of the four chiral centres: the branching alkyl centre was that produced by KS1 and, surprisingly, both hydroxyl centres produced by the reduction steps carried out by KR5 and KR6 respectively [16].
• Carboxypeptidase-A and a monoclonal antibody (KS1/4) directed against a human lung carcinoma cell line (UCLA-P3) were derivatized by treatment with succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate and N-succinimidyl 3-(2-pyridyldithio)propionate, respectively [17].
• DMSO-induced changes in surface expression of CD4, CD44, and KS-1 were reversible over time upon removal of DMSO from the culture medium [18].

Other interactions of CXCL14

• By contrast, BLC mRNA was not detected in either group of mice, and BMAC mRNA was highly up-regulated in late stage of infection with the non-lethal Eg101 strain relative to levels in NY strain-infected mice [19].
• Chemokines do not induce mast cell degranulation but CXCL14 causes secretion of de novo synthesized CXCL8 [20].
• A comparison of genes transcriptionally up-regulated in senescence to those in which expression is significantly down-regulated in immortalized HPECs identified three genes: the chemokine BRAK, DOC1, and a member of the insulin-like growth factor axis, IGFBP-3 [21].

Analytical, diagnostic and therapeutic context of CXCL14

• LAPC4 cells expressing CXCL14 resulted in a 43% tumor growth inhibition (P = 0.019) in vivo compared to vector only xenografts [2].
• METHODS: Real-time quantitative RT-PCR, in situ RNA hybridization, laser capture microscopy, immunohistochemistry, and cDNA array based technologies were used to examine CXCL14 (BRAK) expression in paired normal and tumor prostate [2].
• As determined by ELISA, the binding properties of KS1/4-DAVLB to tumor antigens were not affected by pH or temperature [22].
• EpCAM expression was determined by immunohistochemistry using both huKS-IL2 and the parent KS1/4 antibody [23].
• The tissue and tumor distribution of the antigen recognized by monoclonal antibody KS1/4 was determined by a combination of immunoperoxidase techniques, flow cytometric analyses and solid phase enzyme-linked immunoassays [24].

References