Dataset Information

Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

ABSTRACT:

Objective

Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins between these two types of MSCs.

Materials and methods

In this experimental study, MSC-like cells derived from benign (pleomorphic adenoma, n=5) and malignant (mucoepidermoid carcinoma, n=5) tumor tissues were verified by fluorochrome antibodies and flow cytometric analysis. Differentially expressed proteins were identified using two-dimensional polyacrylamide gel electrophoresis (2DE) and Mass spectrometry.

Results

Results showed that isolated cells strongly expressed characteristic MSCs markers such as CD44, CD73, CD90, CD105, and CD166, but they did not express or weakly expressed CD14, CD34, CD45 markers. Furthermore, the expression of CD24 and CD133 was absent or near absent in both isolated cells. Results also discovered overexpression of Annexin A4 (Anxa4), elongation factor 1-delta (EF1-D), FK506 binding protein 9 (FKBP9), cytosolic platelet-activating factor acetylhydrolase type IB subunit beta (PAFAH1B), type II transglutaminase (TG2), and s-formylglutathione hydrolase (FGH) in MSCs isolated from the malignant tissues. Additionally, heat shock protein 70 (Hsp70), as well as keratin, type II cytoskeletal 7 (CK-7), were found to be overexpressed in MSCs derived from the benign ones.

Conclusion

Malignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy.

SUBMITTER: Haghshenas MR

PROVIDER: S-EPMC9124444 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

Haghshenas Mohammad Reza MR Erfani Nasrollah N Khansalar Soolmaz S Khademi Bijan B Ashraf Mohammad Javad MJ Razmkhah Mahboobeh M Ghaderi Abbas A

Cell journal 20220427 4

<h4>Objective</h4>Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins between these two types of MS ...[more]

PMID: 35674025

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Project description:Rationale: Immunosuppression in the tumor microenvironment (TME) is key to the pathogenesis of solid tumors. Tumor cell-intrinsic autophagy is critical for sustaining both tumor cell metabolism and survival. However, the role of autophagy in the host immune system that allows cancer cells to escape immune destruction remains poorly understood. Here, we determined if attenuated host autophagy is sufficient to induce tumor rejection through reinforced adaptive immunity. Furthermore, we determined whether dietary glutamine supplementation, mimicking attenuated host autophagy, is capable of promoting antitumor immunity. Methods: A syngeneic orthotopic tumor model in Atg5+/+ and Atg5flox/flox mice was established to determine the impact of host autophagy on the antitumor effects against mouse malignant salivary gland tumors (MSTs). Multiple cohorts of immunocompetent mice were used for oncoimmunology studies, including inflammatory cytokine levels, macrophage, CD4+, and CD8+ cells tumor infiltration at 14 days and 28 days after MST inoculation. In vitro differentiation and in vivo dietary glutamine supplementation were used to assess the effects of glutamine on Treg differentiation and tumor expansion. Results: We showed that mice deficient in the essential autophagy gene, Atg5, rejected orthotopic allografts of isogenic MST cells. An enhanced antitumor immune response evidenced by reduction of both M1 and M2 macrophages, increased infiltration of CD8+ T cells, elevated IFN-γ production, as well as decreased inhibitory Tregs within TME and spleens of tumor-bearing Atg5flox/flox mice. Mechanistically, ATG5 deficiency increased glutamine level in tumors. We further demonstrated that dietary glutamine supplementation partially increased glutamine levels and restored potent antitumor responses in Atg5+/+ mice. Conclusions: Dietary glutamine supplementation exposes a previously undefined difference in plasticity between cancer cells, cytotoxic CD8+ T cells and Tregs.

Project description:Purpose The clinical practice of elastosonography for the detection of salivary gland tumors is still a controversial issue. The objective of this meta-analysis was to evaluate the effect of elastosonography for the diagnosis of salivary gland tumors and to compare the diagnostic value of elastosonography and conventional ultrasound in the diagnosis of salivary gland tumors. Methods A comprehensive literature search through PubMed, EMBASE, and Cochrane Library was carried out from inception to November 2021. Two researchers independently extracted the data from the enrolled papers using a standard data extraction form. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic performance of elastosonography. The Quality Assessment of Diagnostic Accuracy Studies—2 (QUADAS-2) tool was utilized to evaluate the quality of each included study. Meta-DiSc version 1.4, Review Manager 5.3, and StataSE 15 were used. Results Sixteen studies with a total of 1105 patients with 1146 lesions were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of elastosonography for the differentiation between benign and malignant salivary gland tumors were 0.73 (95%CI, 0.66–0.78), 0.64 (95%CI, 0.61–0.67), 2.83 (95%CI, 1.97–4.07), 0.45 (95%CI, 0.32–0.62), and 9.86 (95%CI, 4.49–21.62), respectively, with an AUC of 0.82. Four studies provided data regarding the conventional ultrasound for the differentiation between benign and malignant salivary gland tumors. The pooled sensitivity, specificity, and DOR were 0.62 (95%CI, 0.50–0.73), 0.93 (95%CI, 0.90–0.96), and 25.07 (95%CI, 4.28–146.65), respectively. The meta-regression and subgroup analyses found that assessment methods were associated with significant heterogeneity, and quantitative or semiquantitative elastosonography performed better than the qualitative one. Conclusions Elastosonography showed a limited value for diagnosing malignant salivary gland tumors; it could be considered as a supplementary diagnostic technology to conventional ultrasound, and quantitative or semiquantitative elastosonography was superior to the qualitative one.

Dataset Information

Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

Objective

Materials and methods

Results

Conclusion

Publications

Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors.

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