Expression of Interleukin-1ß and Interleukin-8 in Oral Potentially Malignant Disorders and Carcinomas

López-Labady, Jeaneth; Bologna‐Molina, Ronell; Dorrego, Mariana Villarroel

doi:10.3389/froh.2021.649406

Cited by 8 publications

(5 citation statements)

References 36 publications

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“…To elucidate the mechanism by which OSCC cells regulate p‐ACLY level and lipid synthesis in fibroblasts, we searched for exocrine molecules of OSCC cells that can function as AKT agonists. Interleukin‐8 (IL8) was identified in previously published reports as a possible upstream regulator 31–35 . We examined IL8 expression in The Cancer Genome Atlas database using the GEPIA website.…”

Section: Resultsmentioning

confidence: 99%

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Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer‐associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p‐ACLY axis

Liu,

Wang,

et al. 2024

Cancer Science

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Lipid metabolic reprogramming of tumor cells has been proven to play a critical role in tumor initiation and development. However, lipid metabolism in cancer‐associated fibroblasts (CAFs) has rarely been studied, particularly in CAFs of oral squamous cell carcinoma (OSCC). Additionally, the molecular mechanism by which tumor cells regulate lipid metabolism in fibroblasts is unclear. In this study, we found that phosphorylated ATP citrate lyase (p‐ACLY), a key lipid metabolic enzyme, was upregulated in OSCC CAFs. Compared to paracancerous normal fibroblasts, CAFs showed enhanced lipid synthesis, such as elevated cytosolic acetyl‐CoA level and accumulation of lipid droplets. Conversely, reduction of p‐ACLY level blocked this biological process. In addition, blocking lipid synthesis in CAFs or inhibiting fatty acid uptake by OSCC cells reduced the promotive effects of CAFs on OSCC cell proliferation, invasion, and migration. These findings suggested that CAFs are one of lipid sources required for OSCC progression. Mechanistically, AKT signaling activation was involved in the upregulation of p‐ACLY level and lipid synthesis in CAFs. Interleukin‐8 (IL8), an exocrine cytokine of OSCC cells, could activate AKT and then phosphorylate ACLY in fibroblasts. This study suggested that the IL8/AKT/p‐ACLY axis could be considered as a potential target for OSCC treatment.

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Section: Resultsmentioning

confidence: 99%

“…Interleukin‐8 (IL8) was identified in previously published reports as a possible upstream regulator. 31 , 32 , 33 , 34 , 35 We examined IL8 expression in The Cancer Genome Atlas database using the GEPIA website. Results indicated that IL8 was upregulated in head and neck squamous cell carcinoma tissues (Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer‐associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p‐ACLY axis

Liu,

Wang,

et al. 2024

Cancer Science

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“…To elucidate the mechanism by which OSCC cells regulate p-ACLY level and lipid synthesis in broblasts, we reviewed the literature and searched for exocrine molecules that are highly expressed in OSCC cells and can function as AKT agonists. As a result, IL8 was identi ed in the literature as a possible upstream regulator [29][30][31][32]. Then we examined IL8 expression in the TCGA database using the Gene Expression Pro ling Analysis (GEPIA) website.…”

Section: Resultsmentioning

confidence: 99%

“…It has now been shown that IL8 is not only an in ammatory chemokine, but also a pro-cancer factor. Substantial elevation of IL8 expression was detected in various types of cancer including OSCC, and IL8 has been reported to stimulate angiogenesis, recruit immunosuppressive cells, promote epithelial-to-mesenchymal transition, and enhance stemness and chemoresistance of tumor cells [30,[36][37][38][39]. Notably, activation of AKT signaling is one of the major mechanisms by which IL8 regulates the phenotype and function of tumor and stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Enhanced lipid biosynthesis in OSCC cancer associated fibroblasts contributes to tumor progression: role of IL8/AKT/p-ACLY axis

Liu,

Wang,

et al. 2023

Preprint

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Background ATP citrate lygase (ACLY), the key enzyme regulating lipid synthesis, has been proven to play a critical role in tumor initiation and development. However, the roles and relevant mechanisms of ACLY in cancer associated fibroblasts (CAFs) have rarely been studied, particularly in CAFs of oral squamous cell carcinoma (OSCC). Plus, the molecular mechanism by which tumor cells regulate ACLY in fibroblasts is unclear. Methods IHC staining, PCR and Western blot were employed to detect ACLY expression pattern in OSCC tissues and OSCC primary CAFs. The biological roles and relevant mechanisms of ACLY in OSCC CAFs were investigated by in vitro and in vivo experiments. Results The phosphorylated ACLY (p-ACLY) was highly expressed in OSCC CAFs and CAFs underwent enhanced lipid synthesis, including elevated intracellular level of acetyl-CoA and accumulation of lipid droplets. Conversely, inhibition of p-ACLY blocked this biological process. Moreover, blocking lipid synthesis in CAFs or inhibiting fatty acid uptake by OSCC cells reduced the promotive effects of CAFs on OSCC cell proliferation, invasion and migration. These results suggested that CAFs served as one of lipid sources for OSCC cells during tumor progression. Mechanistically, AKT signaling activation was involved in the elevations of p-ACLY level and lipid synthesis in CAFs. IL8 was an exocrine cytokine of OSCC cells that could activate AKT and then phosphorylate ACLY in fibroblasts. Conclusions P-ACLY positively regulated lipid synthesis of OSCC CAFs, making CAFs one of the lipid sources required for tumor progression. IL8 was an exocrine cytokine of OSCC cells that could upregulate p-ACLY level and lipid synthesis in fibroblasts via AKT signaling activation. Therefore, the IL8/AKT/p-ACLY axis could be considered as a potential therapeutic target for OSCC treatment.

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“…Galectin-3 may be upregulated in COVID-19 cohorts (A1,2,3) but the amount found in saliva were near saturation for the GCFP assay as configured. Finally, IL-8 cytokines are produced by a wide range of cells including oral keratinocytes and are a potential biomarker for predicting oral disease (Finoti et al, 2017;Lopez-Labady et al, 2021). IL-8 was also reported early in the pandemic to be a sensitive serum biomarker in both mild and severe COVID-19 patients .…”

Section: Discussionmentioning

confidence: 98%

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C

Maltz-Matyschsyk

Melchiorre

Herbst

et al. 2023

Front. Bioeng. Biotechnol.

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Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4–6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5–13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80 μL of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.

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Expression of Interleukin-1ß and Interleukin-8 in Oral Potentially Malignant Disorders and Carcinomas

Cited by 8 publications

References 36 publications

Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer‐associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p‐ACLY axis

Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer‐associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p‐ACLY axis

Enhanced lipid biosynthesis in OSCC cancer associated fibroblasts contributes to tumor progression: role of IL8/AKT/p-ACLY axis

Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C

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