Dataset Information

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

ABSTRACT: Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.

SUBMITTER: Shahrabi-Farahani S

PROVIDER: S-EPMC4822338 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Shahrabi-Farahani Shokoufeh S Gallottini Marina M Martins Fabiana F Li Erik E Mudge Dayna R DR Nakayama Hironao H Hida Kyoko K Panigrahy Dipak D D'Amore Patricia A PA Bielenberg Diane R DR

The American journal of pathology 20160211 4

Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor loca ...[more]

PMID: 26877262

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Project description:ObjectiveMUCIN4 (MUC4) glycosylation is linked to the oncogenesis and progression of a neoplastic process. It can suggest information pertaining to tumor progression, management and its natural properties. Thus, MUC4 can play a pivotal role in prognostic diagnosis. This study aimed to analyze the MUC4 expression in oral cell squamous carcinoma and oral dysplastic epithelium.Materials and methodsThe research included 45 samples of oral epithelial dysplasia (OED) and 45 cases of oral squamous cell carcinoma (OSCC). In order to carry out the investigation, tissue blocks of previously diagnosed cases of OED and OSCC were retrieved from the relevant archives. Forty-five OED cases were categorized into three group's mild, moderate and severe dysplasia, with 15 cases in each respective category. Forty-five OSCC cases were categorized into three groups: well differentiated, moderately differentiated, and poorly differentiated OSCC with 15 cases in each respective category. Ten tissue biopsies of normal oral mucosa were obtained from subjects in the control group. The chi-square test and one-way ANOVA were used for statistical analysis.ResultThere was an absence of MUC4 expression in normal mucosa, whereas the OED and OSCC groups had a significant amount of observable variance. Within the OED category of cases, a consistent progression from mild to severe dysplasia was seen in terms of the staining pattern. Cases with severe dysplasia displayed a staining pattern that covered the complete thickness of the tissue in the epithelium. Expression of MUC4 was shown to be lower in moderate differentiated squamous cell carcinoma (MDSCC), and poorly differentiated squamous cell carcinoma (PDSCC) as compared to well differentiated squamous cell carcinoma (WDSCC). It showed decreasing pattern across all grades of OSCC. In WDSCC, an intense highest staining response was noticed, particularly among the cells that are highly differentiated and take the form of a honeycomb pattern.ConclusionAnalysis of the expression profile of MUC4 and the aberrant expression of this gene in OSCC suggests that it may serve as a useful diagnostic marker. Therefore, it is possible to draw the conclusion that MUC4 plays a very significant part in the pathogenesis of OSCC and also acts as a marker that may be taken into consideration for the accurate diagnosis of OED and OSCC.

Project description:Oral squamous cell carcinoma (OSCC) ranks among the top ten most prevalent cancers worldwide. Like most head and neck squamous cell carcinomas (HNSCCs), OSCC is highly inflammatory and aggressive. However, the signaling pathways triggering the activation of its inflammatory processes remain elusive. G protein-coupled receptor signaling regulates the inflammatory response and invasiveness of cancers, but it remains unclear whether G?12 is a critical player in the inflammatory cytokine pathway during the tumorigenesis of OSCC. This study was undertaken to determine the role of G?12 signaling in the regulation of proinflammatory cytokines in their mediation of OSCC invasion. We found that both the transcription and protein levels of G?12 are up-regulated in OSCC tumors. The elevated G?12 expressions in OSCC patients also correlated with extra-capsular spread, an indicator of tumor invasiveness in HNSCCs. This clinical finding was supported by the studies of overexpression and RNAi knockdown of G?12 in OSCC cells, which demonstrated that G?12 promoted tumor cell migration and invasion. To understand how G?12 modulates OSCC invasiveness, we analyzed key biological processes in microarray data upon depletion of G?12 and found that cytokine- and other immune-related pathways were severely impaired. Importantly, the mRNA levels of IL-6 and IL-8 proinflammatory cytokines in clinical samples were found to be significantly correlated with the increased G?12 levels, suggesting a potential role of G?12 in modulating the IL-6 and IL-8 expressions. Supporting this hypothesis, overexpression or RNAi knockdown of G?12 in OSCC cell lines both showed that G?12 positively regulated the mRNA and protein levels of IL-6 and IL-8. Finally, we demonstrated that the G?12 promotion of tumor cell invasiveness was suppressed by the neutralization of IL-6 and IL-8 in OSCC cells. Together, these findings suggest that G?12 drives OSCC invasion through the up-regulation of IL-6 and IL-8 cytokines.

Dataset Information

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Publications

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

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