title: Receptors for hyaluronic acid and poliovirus: a combinatorial role in glioma invasion?
abstract: BACKGROUND
  CD44 has long been associated with glioma invasion while, more recently, CD155 has been implicated in playing a similar role. Notably, these two receptors have been shown closely positioned on monocytes.
  
  
  RESULTS
  In this study, an up-regulation of CD44 and CD155 was demonstrated in established and early-passage cultures of glioblastoma. Total internal reflected fluorescence (TIRF) microscopy revealed close proximity of CD44 and CD155. CD44 antibody blocking and gene silencing (via siRNA) resulted in greater inhibition of invasion than that for CD155. Combined interference resulted in 86% inhibition of invasion, although in these investigations no obvious evidence of synergy between CD44 and CD155 in curbing invasion was shown. Both siRNA-CD44 and siRNA-CD155 treated cells lacked processes and were rounder, while live cell imaging showed reduced motility rate compared to wild type cells. Adhesion assay demonstrated that wild type cells adhered most efficiently to laminin, whereas siRNA-treated cells (p<0.0001 for both CD44 and CD155 expression) showed decreased adhesion on several ECMs investigated. BrdU assay showed a higher proliferation of siRNA-CD44 and siRNA-CD155 cells, inversely correlated with reduced invasion. Confocal microscopy revealed overlapping of CD155 and integrins (β(1), α(v)β(1) and α(v)β(3)) on glioblastoma cell processes whereas siRNA-transfected cells showed consequent reduction in integrin expression with no specific staining patterns. Reduced expression of Rho GTPases, Cdc42, Rac1/2/3, RhoA and RhoB, was seen in siRNA-CD44 and siRNA-CD155 cells. In contrast to CD44-knockdown and 'double'-knockdown cells, no obvious decrease in RhoC expression was observed in CD155-knockdown cells.
  
  
  CONCLUSIONS
  This investigation has enhanced our understanding of cell invasion and confirmed CD44 to play a more significant role in this biological process than CD155. Joint CD44/CD155 approaches may, however, merit further study in therapeutic targeting of infiltrating glioma cells.
authors.affiliation: Cellular and Molecular Neuro-oncology Research Group, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom.
authors.forename: Zaynah
authors.initials: Z
authors.lastname: Maherally
authors.forename: James R
authors.initials: JR
authors.lastname: Smith
authors.forename: Qian
authors.initials: Q
authors.lastname: An
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Pilkington
mesh_terms: D000199:Actins / Q000378:metabolism; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D017955:Poliovirus / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D016023:Integrins; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C066100:poliovirus receptor; D006820:Hyaluronic Acid; D020741:rho GTP-Binding Proteins