title: CXCL14 enhances proliferation and migration of NCI-H460 human lung cancer cells overexpressing the glycoproteins containing heparan sulfate or sialic acid.
abstract: CXCL14 is a chemokine family member that is involved in various cellular responses in addition to immune cell activation. Although constitutive CXCL14 expression in normal epithelial cells may help protect against infection by activating immune systems, its expression in cancer cells has raised controversy regarding its possible role in tumorigenesis. However, the underlying mechanisms for this disparity remain unknown. Investigation of cellular CXCL14 binding properties might increase our understanding of the peptide's roles in tumorigenesis. In the present study, we found that CXCL14 binds to various cell types. Interestingly, binding to NCI-H460 cells was prevented by heparan sulfate and N-acetyl neuraminic acid. Next, we examined effect of CXCL14 binding in NCI-H460 and NCI-H23. CXCL14 enhanced proliferation and migration in NCI-H460 but had no effect on NCI-H23. A reporter gene assay with various transcription factor response elements revealed that only nuclear factor-κB (NF-κB) signaling was activated by CXCL14 in NCI-H460 cells, which was blocked by BAPTA-AM, TPCA-1, and brefeldin A. Exogenous expression of some glycoproteins such as syndecan-4, podoplanin, and CD43 in these cells enhanced CXCL14 binding and NF-κB activity. Collectively, these results demonstrate that CXCL14 binding to glycoproteins harboring heparan sulfate proteoglycans and sialic acids leads proliferation and migration of some cancer cells.
authors.affiliation: Graduate School of Medicine; Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705, Republic of Korea.
authors.forename: Cho Rong
authors.initials: CR
authors.lastname: Park
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: You
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Kim
authors.forename: Mi Jin
authors.initials: MJ
authors.lastname: Moon
authors.forename: Cheolju
authors.initials: C
authors.lastname: Lee
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Seong
authors.forename: Jong-Ik
authors.initials: JI
authors.lastname: Hwang
mesh_terms: D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D019743:Chemokines, CXC / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism*; D057809:HEK293 Cells; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011961:Receptors, Fc / Q000378:metabolism
chemical_list: D019743:Chemokines, CXC; D006023:Glycoproteins; D006497:Heparan Sulfate; D019158:N-Acetylneuraminic Acid; D016328:NF-kappa B; D011961:Receptors, Fc; C118056:CXCL14 protein, human