Increased ICAM-1 expression in transformed human oral epithelial cells: molecular mechanism and functional role in peripheral blood mononuclear cell adhesion and lymphokine-activated-killer cell cytotoxicity.

Huang, George T.‐J.; Zhang, Xinli; Park, No-Hee

doi:10.3892/ijo.17.3.479

Cited by 24 publications

(27 citation statements)

References 35 publications

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“…Attachment of cancer cells to the "injured" endothelium, expressing E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), seems to be initiated by multiple interactions between selectins and the oligosaccharide ligand sialyl Lewis X, expressed on circulating vascular and tumor cells (36). This is followed by subsequent firm adhesion of tumor cells via integrins (36)(37)(38)(39), allowing them to emigrate into tissue. In this study, we characterized a new role of eRNA in this multistep process.…”

Section: Discussionmentioning

confidence: 99%

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

et al. 2013

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Extracellular RNA (eRNA) released from injured cells promotes tissue permeability, thrombosis, and inflammation in vitro and in vivo, and RNase1 pretreatment can reduce all these effects. In this study, we investigated the role of the eRNA/RNase1 system in tumor progression and metastasis. Under quiescent and stimulatory conditions, tumor cells released much higher levels of endogenous extracellular RNA (eRNA) than nontumor cells. In glioblastomas, eRNA was detected at higher levels in tumors than nontumor tissue. eRNA induced tumor cells to adhere to and migrate through human cerebral microvascular endothelial cells (HCMEC/D3), in a manner requiring activation of VEGF signaling. In addition, eRNA liberated TNF-a from macrophages in a manner requiring activation of the TNF-a-converting enzyme TACE. Accordingly, supernatants derived from eRNAtreated macrophages enhanced tumor cell adhesion to HCMEC/D3. TNF-a release evoked by eRNA relied upon signaling activation of mitogen-activated protein kinases and the NF-kB pathway. In subcutaneous xenograft models of human cancer, administration of RNase1 but not DNase decreased tumor volume and weight. Taken together, these results suggest that eRNA released from tumor cells has the capacity to promote tumor cell invasion through endothelial barriers by both direct and indirect mechanisms, including through a mechanism involving TNF-a release from tumor-infiltrating monocytes/macrophages. Our findings establish a crucial role for eRNA in driving tumor progression, and they suggest applications for extracellular RNase1 as an antiinvasive regimen for cancer treatment. Cancer Res; 73(16); 5080-9. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

et al. 2013

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“…Consequently, KSHV lytic replication is studied through reactivation, which requires one or more chem- (25). It is not fully transformed, maintains some features of primary cells, and has been used for studying pathogen-host interaction, innate immune response, differentiation, apoptosis, and tumorigenesis (41)(42)(43)(44)(45)(46)(47)(48)(49). As saliva is the major source of transmission for KSHV and epithelial cells may play an important role in producing infectious virions, we sought to identify an oral epithelial cell line that can support robust lytic replication of KSHV.…”

Section: Discussionmentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus ORF18 and ORF30 Are Essential for Late Gene Expression during Lytic Replication

Gong

Xie

et al. 2014

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human malignances. As saliva is likely the major vehicle for KSHV transmission, we studied in vitro KSHV infection of oral epithelial cells. Through infection of two types of oral epithelial cells, normal human oral keratinocytes (NHOKs) and papilloma-immortalized human oral keratinocyte (HOK16B) cells, we found that KSHV can undergo robust lytic replication in oral epithelial cells. By employing de novo lytic infection of HOK16B cells, we studied the functions of two previously uncharacterized genes, ORF18 and ORF30, during the KSHV lytic cycle. For this purpose, an ORF18-deficient virus and an ORF30-deficient virus were generated using a mutagenesis strategy based on bacterial artificial chromosome (BAC) technology. We found that neither ORF18 nor ORF30 is required for immediately early or early gene expression or viral DNA replication, but each is essential for late gene expression during both de novo lytic replication and reactivation. This critical role of ORF18 and ORF30 in late gene expression was also observed during KSHV reactivation. In addition, global analysis of viral transcripts by RNA sequencing indicated that ORF18 and ORF30 control the same set of viral genes. Therefore, we suggest that these two viral ORFs are involved in the same mechanism or pathway that coregulates the viral late genes as a group. IMPORTANCEWhile KSHV can infect multiple cell types in vitro, only a few can support a full lytic replication cycle with progeny virions produced. Consequently, KSHV lytic replication is mostly studied through reactivation, which requires chemicals to induce the lytic cycle or overexpression of the viral transcriptional activator, RTA. In this study, we present a robust de novo lytic infection system based on oral epithelial cells. Using this system, we demonstrate the role of two viral ORFs, ORF18 and ORF30, in regulating viral gene expression during KSHV lytic replication. As the major route of KSHV transmission is thought to be via saliva, this new KSHV lytic replication system will have important utility in the field.

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“…The signals were visualized by autoradiography as described above. The half-lives of HBD-2 transcripts were measured by comparison with the mRNA level at time 0 (100%) as described [61]. …”

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confidence: 99%

Capacity of human β-defensin expression in gene-transduced and cytokine-induced cells

Yin¹,

Dang²,

Zhang³

et al. 2006

Biochemical and Biophysical Research Communications

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The purpose of this study was to determine the capacity of cells transduced with human β-defensins (HBDs) to express antimicrobial peptides, since sufficient expression level is required for effective antimicrobial activity. Retroviral vector pBabeNeo and lentiviral vector SIN18cPPTRhMLV (SIN18) carrying HBDs were utilized to transduce non-HBD-expressing cells such as fibroblasts or HBD-producing oral epithelial cells. We found that HBD-3 gene transfer to fibroblasts was possible not via retrovirus but by direct vector transfection. SIN18 had high transduction efficiencies (80.9-99.9%) and transduced cells expressed higher amounts of HBD-2 than those by pBabe-Neo. Primary human gingival epithelial cells (HGECs) expressed greater amounts of HBD-2 than primary fibroblasts after lentiviral transduction. Additionally, HBD-2 secretion from transduced HGECs cells was further increased when stimulated with IL-1 or TNFα. Our data indicate that while HBD-2 expression is limited in primary fibroblasts, its expression in HGECs may be maximized by gene transduction plus cytokine induction. KeywordsHBD-2; HBD-3; Lentiviral vectors; Retroviral vectors; IL-1; TNFα; Gingival epithelial cells Natural antimicrobial peptides have been considered as an alternative option for infection control due to the increasing resistance of microbes to conventional antibiotics. Because some potent antimicrobial peptides are encoded by single genes, the possibility of artificially delivering these genes into tissues/organs to augment innate immunity against infection or creating transgenic animals to produce antimicrobial peptides has been explored [1][2][3][4][5]. Subsequently, the term antimicrobial gene therapy has emerged [6] and engineered skin NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript models have been used to test the concept of antimicrobial gene therapy both in vitro and in vivo [7,8]. Human β-defensins (HBDs or DEFB) and cathelicidin LL37 are being actively used as study models for their potent ability to kill a broad spectrum of bacteria and fungi [6,7,[9][10][11][12][13], as well as to inhibit viral infections [14,15]. HBDs are expressed mostly in epithelia [11,12,[16][17][18][19][20][21][22][23][24]. Besides the cloned, sequenced, and well-characterized HBD-1, -2, -3, and -4, there appears to be at least 28 more HBDs existing based on the genomic surveys using computational search strategy [25][26][27]. Fourteen HBDs or DEFB gene transcripts (DEFB-1, -4, and DEFB-103 to -114) were investigated using reverse transcriptionpolymerase chain reaction (RT-PCR) to detect their expression in gingival keratinocytes and a selected few have been classified as constitutive or inducible [27].HBDs are considered to play an important role in epithelial defense mechanism and the regulation of their expression in diseased conditions is being actively investigated. Bacteria and cytokines IL-1 and TNFα upregulate HBD-2 expression in lung and skin epithelial cells [10,28] and induction of HBDs by these stimuli is...

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Increased ICAM-1 expression in transformed human oral epithelial cells: molecular mechanism and functional role in peripheral blood mononuclear cell adhesion and lymphokine-activated-killer cell cytotoxicity.

Cited by 24 publications

References 35 publications

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

Extracellular RNA Liberates Tumor Necrosis Factor-α to Promote Tumor Cell Trafficking and Progression

Kaposi's Sarcoma-Associated Herpesvirus ORF18 and ORF30 Are Essential for Late Gene Expression during Lytic Replication

Capacity of human β-defensin expression in gene-transduced and cytokine-induced cells

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