Low COX2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progression

Vandoros, Gerasimos P.; Kourelis, Theodoros; Papadas, Theodoros; Goumas, Panos; Sotiropoulou-Bonikou, Georgia

doi:10.1002/lary.20569

Cited by 15 publications

(12 citation statements)

References 26 publications

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“…In addition to its role in inflammation, PGE2 promotes angiogenesis by inducing endothelial cell growth, tumor migration and proliferation [11]. As a result of these properties, COX2 activity in the stroma is correlated with worse tumor grade in various cancers, but specifically in HNSCC [45]. These results suggest that COX2 inhibitors should have value as anti-cancer agents, but more specific inhibition of microsomal PGE synthase might be an even better line of attack [11].…”

Section: Interactions Between Tafs and Immune Cellsmentioning

confidence: 99%

Molecular communication between tumor-associated fibroblasts and head and neck squamous cell carcinoma

Leef

Thomas

2013

Oral Oncology

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Over the past few decades, it has become increasingly clear that the lethality of cancers depends on more than the malignant cells themselves. The environment those malignant cells are exposed to is just as important a determinant of their behavior. Head and neck squamous cell carcinoma (HNSCC) is both common and deadly. It is the 6 th most frequently occurring cancers, and prognosis is still generally poor. Recent evidence indicates that activated fibroblasts residing within the tumor stroma play a significant role in promoting the aggressive spread often seen in head and neck cancer. Tumor associated fibroblasts (TAFs) have also been implicated in facilitating angiogenesis and suppressing the normal anti-tumor function of immune cells. Studying the signaling molecules involved in these processes will facilitate the development of promising targets and inhibitors to prevent tumor-associated fibroblasts from exerting their reinforcing effects on the tumor. In this article, we review the recent literature on the signals used in tumor associated fibroblast communication, with a focus on potential therapeutic targets. Further, we highlight the lead candidates for TAF-targeted therapeutic interventions. Future anticancer strategies may achieve better results than current approaches by targeting the support cells in tumor stroma in addition to the cancerous cells.

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Section: Interactions Between Tafs and Immune Cellsmentioning

confidence: 99%

Molecular communication between tumor-associated fibroblasts and head and neck squamous cell carcinoma

Leef

Thomas

2013

Oral Oncology

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“…The overexpression of COX-2 is associated with various types of cancer and the expression levels are generally proportional to cancer aggressiveness [ 55 , 56 ]. Low COX-2 expression in epithelial cells and upregulation in stroma, however, has been shown to be indicative of tumor progression in laryngeal squamous cell carcinoma [ 57 ]. The significance of COX-2 as a driver of tumorigenesis illustrates that differential proteomic approaches investigating broader downstream implications of key transcriptional modulators, as taken in this study, may reveal key microenvironmental association ultimately contributing to clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Stromal TRIM28-associated signaling pathway modulation within the colorectal cancer microenvironment

et al. 2018

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BackgroundStromal gene expression patterns predict patient outcomes in colorectal cancer. TRIM28 is a transcriptional co-repressor that regulates an abundance of genes through the KRAB domain family of transcription factors. We have previously shown that stromal expression of TRIM28 is a marker of disease relapse and poor survival in colorectal cancer. Here, we perform differential epithelium-stroma proteomic network analyses to characterize signaling pathways associated with TRIM28 within the tumor microenvironment.MethodsReverse phase protein arrays were generated from laser capture micro-dissected carcinoma and stromal cells from fresh frozen colorectal cancer tissues. Phosphorylation and total protein levels were measured for 30 cancer-related signaling pathway endpoints. Strength and direction of associations between signaling endpoints were identified using Spearman’s rank-order correlation analysis and compared to TRIM28 levels. Expression status of TRIM28 in tumor epithelium and stromal fibroblasts was assessed using IHC in formalin fixed tissue and the epithelium to stroma protein expression ratio method.ResultsWe found distinct proteomic networks in the epithelial and stromal compartments which were linked to expression levels of TRIM28. Low levels of TRIM28 in tumor stroma (high epithelium: stroma ratio) were found in 10 out of 19 cases. Upon proteomic network analyses, these stromal high ratio cases revealed moderate signaling pathway similarity exemplified by 76 significant Spearman correlations (ρ ≥ 0.75, p ≤ 0.01). Furthermore, low levels of stromal TRIM28 correlated with elevated MDM2 levels in tumor epithelium (p = 0.01) and COX-2 levels in tumor stroma (p = 0.002). Low TRIM28 epithelium to stroma ratios were associated with elevated levels of caspases 3 and 7 in stroma (p = 0.041 and p = 0.036) and an increased signaling pathway similarity in stromal cells with 81 significant Spearman correlations (ρ ≥ 0.75, p ≤ 0.01).ConclusionsBy dissecting TRIM28-associated pathways in stromal fibroblasts and epithelial tumor cells, we performed comprehensive proteomic analyses of molecular networks within the tumor microenvironment. We found modulation of several signaling pathways associated with TRIM28, which may be attributed to the pleiotropic properties of TRIM28 through its translational suppression of the family of KRAB domain transcription factors in tumor stromal compartments.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1465-z) contains supplementary material, which is available to authorized users.

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“…18 The disease free survival was significantly higher with stronger Cox-2 expression in a retrospective analysis of 97 cases of laryngeal cancer, although they had proved a higher grade of tumor with low Cox-2 expression. 19 There is paucity of literature on the role of Cox-2 in predicting treatment failure after primary surgery, followed by chemo radiation. The overexpression of Cox-2 was found to be a predictor of increased risk of local recurrence after radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2 expression in squamous cell carcinoma of larynx: association with clinico-pathological factors and treatment outcomes

Iype

Balakrishna

Subhadradevi

et al. 2018

Int J Otorhinolaryngol Head Neck Surg

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Background: Squamous cell carcinoma (SCC) of larynx is widely prevalent in India and is one of the leading cancers in males. Tumor Cyclooxygenase-2 (Cox-2) expression can be used as a prognostic and predictive marker in laryngeal SCC. The primary objective of the present study was to determine the association between tumor Cox-2 expression and clinico-pathological characteristics and treatment outcome in patients with LSCC. Secondly, to evaluate the clinical utility of Cox-2 expression as a tool, to decide treatment strategy for LSCC.Methods: Seventy two patients with stage III and IV LSCC who underwent upfront surgery were included in this study. Tumor Cox-2 expression was analysed by immunohistochemistry using standard Streptavidin biotin method. Results: Thirty seven patients had pathological node involvement, ipsilateral in 35 and bilateral in two. Cox-2 was intensely expressed in patients with advanced (N2/N3) nodal disease and perineural invasion. There was no significant difference in 5 year disease free survival and overall survival when Cox-2 was correlated with perineural invasion, extra capsular spread and the T and N stage of the disease.Conclusions: Preoperative Cox-2 analysis can be used to individualize need for routine neck dissection in cases of locally advanced laryngeal carcinoma.

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Low COX2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progression

Cited by 15 publications

References 26 publications

Molecular communication between tumor-associated fibroblasts and head and neck squamous cell carcinoma

Molecular communication between tumor-associated fibroblasts and head and neck squamous cell carcinoma

Stromal TRIM28-associated signaling pathway modulation within the colorectal cancer microenvironment

Cyclooxygenase-2 expression in squamous cell carcinoma of larynx: association with clinico-pathological factors and treatment outcomes

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