Expression of cell adhesion molecules and chemokine receptors: angioinvasiveness in nasal NK/T-cell lymphoma.
Sinonasal natural killer (NK)/T-cell lymphoma (NKTCL) is closely associated with Epstein-Barr virus (EBV) infection and expresses latent membrane protein (LMP)-1 and EB nuclear antigen (EBNA)-1, i.e., latency II of EBV infection. Angioinvasion by neoplastic cells is a characteristic feature of NKTCL, but its mechanism is unknown. To elucidate the molecular mechanism of angio-invasiveness in NKTCL, expression of cell adhesion molecules and chemokine receptors at mRNA and protein levels was examined using real-time PCR and immunohistochemistry in 17 NKTCL together with 10 diffuse large B-cell lymphoma (DLBL) and 9 non-neoplastic nasal mucosa as controls. EBV DNA was detected in 14 of 16 NKTCL examined, and 7 of these 14 expressed LMP-1. mRNA expression levels of integrin subunits alpha4, alpha L, alpha M, and beta2 were significantly higher in NKTCL than non-neoplastic controls. Integrin subunits alpha2 and alpha M were expressed at a significantly higher level in NKTCL with angioinvasion than those without. Expression level of alpha M was significantly higher in 7 cases of NKTCL with LMP-1 expression than 7 without. Immunohistochemistry showed expression of these molecules in NKTCL cells. These findings suggest that EBV infection might be involved in the pathogenesis of angioinvasion of NKTCL through up-regulation of alpha M by LMP-1.
Liu
Angen
A
Department of Pathology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nakatsuka
Shin-Ichi
S
Yang
Woo-Ick
WI
Kojya
Shizuo
S
Aozasa
Katsuyuki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000956:Antigens, Viral / Q000737:chemistry; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009297:Nasal Mucosa / Q000473:pathology; D009389:Neovascularization, Pathologic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000096:biosynthesis; D014764:Viral Proteins / Q000737:chemistry; D017735:Virus Latency
D000956:Antigens, Viral; D017931:DNA Primers; D018076:DNA, Complementary; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D012313:RNA