scholarly journals Involvement of cancer-derived EMT cells in the accumulation of 18F-fluorodeoxyglucose in the hypoxic cancer microenvironment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sachi Sugita ◽  
Masanori Yamato ◽  
Toshimitsu Hatabu ◽  
Yosky Kataoka
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Standardized Uptake Value ◽  
High Rate ◽  
Cancer Microenvironment ◽  
Mesenchymal Transition ◽  
Positron Emission ◽  
Tumor Tissues ◽  
Fluorescence Immunohistochemistry ◽  
Intratumoral Distribution ◽  
Fdg Accumulation

AbstractA high rate of glycolysis, one of the most common features of cancer, is used in positron emission tomography (PET) imaging to visualize tumor tissues using 18F-fluorodeoxyglucose (18F-FDG). Heterogeneous intratumoral distribution of 18F-FDG in tissues has been established in some types of cancer, and the maximum standardized uptake value (SUVmax) has been correlated with poor prognosis. However, the phenotype of cells that show high 18F-FDG accumulation in tumors remains unknown. Here, we combined quantitative micro-autoradiography with fluorescence immunohistochemistry to simultaneously visualize 18F-FDG distribution, the expression of multiple proteins, and hypoxic regions in the cancer microenvironment of a human A431 xenograft tumor in C.B-17/Icr-scid/scid mice. We found that the highest 18F-FDG accumulation was in cancer-derived cells undergoing epithelial-mesenchymal transition (EMT) in hypoxic regions, implicating these regions as a major contributor to increased glucose metabolism, as measured by 18F-FDG-PET.

scholarly journals Oxidized Phospholipids in Tumor Microenvironment Stimulate Tumor Metastasis via Regulation of Autophagy

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 558
Author(s):  
Jin Kyung Seok ◽  
Eun-Hee Hong ◽  
Gabsik Yang ◽  
Hye Eun Lee ◽  
Sin-Eun Kim ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Autophagic Flux ◽  
Oxidized Phospholipids ◽  
Mcf7 Cells ◽  
Mesenchymal Transition ◽  
Tumor Tissues

Oxidized phospholipids are well known to play physiological and pathological roles in regulating cellular homeostasis and disease progression. However, their role in cancer metastasis has not been entirely understood. In this study, effects of oxidized phosphatidylcholines such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) on epithelial-mesenchymal transition (EMT) and autophagy were determined in cancer cells by immunoblotting and confocal analysis. Metastasis was analyzed by a scratch wound assay and a transwell migration/invasion assay. The concentrations of POVPC and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC) in tumor tissues obtained from patients were measured by LC-MS/MS analysis. POVPC induced EMT, resulting in increase of migration and invasion of human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF7). POVPC induced autophagic flux through AMPK-mTOR pathway. Pharmacological inhibition or siRNA knockdown of autophagy decreased migration and invasion of POVPC-treated HepG2 and MCF7 cells. POVPC and PGPC levels were greatly increased at stage II of patient-derived intrahepatic cholangiocarcinoma tissues. PGPC levels were higher in malignant breast tumor tissues than in adjacent nontumor tissues. The results show that oxidized phosphatidylcholines increase metastatic potential of cancer cells by promoting EMT, mediated through autophagy. These suggest the positive regulatory role of oxidized phospholipids accumulated in tumor microenvironment in the regulation of tumorigenesis and metastasis.

scholarly journals Western diet leads to aging-related tumorigenesis via activation of the inflammatory, UPR, and EMT pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ricardo Imbroisi Filho ◽  
Alan C. Ochioni ◽  
Amanda M. Esteves ◽  
João G. B. Leandro ◽  
Thainá M. Demaria ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Western Diet ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation ◽  
Unfolded Protein ◽  
Tissue Microenvironment ◽  
Tumor Tissues ◽  
Causative Factors ◽  
Protein Response

AbstractAmong the principal causative factors for the development of complications related to aging is a diet rich in fats and sugars, also known as the Western diet. This diet advocates numerous changes that might increase the susceptibility to initiate cancer and/or to create a tissue microenvironment more conducive to the growth of malignant cells, thus favoring the progression of cancer and metastasis. Hypercaloric diets in general lead to oxidative stress generating reactive oxygen species and induce endoplasmic reticulum stress. Our results demonstrate that mice bearing tumors fed with a Western diet presented bigger tumor mass with increased insulin sensitivity in these tissues. Several markers of insulin signaling, such as AKT phosphorylation and mTOR pathway, are promoted in tumors of Western diet-fed animals. This process is associated with increased macrophage infiltration, activation of unfolded protein response pathway, and initiation of epithelial–mesenchymal transition (EMT) process in these tumor tissues. Summing up, we propose that the Western diet accelerates the aging-related processes favoring tumor development.

scholarly journals Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1197
Author(s):  
Haoyu Yang ◽  
Zixuan Xu ◽  
Yuqian Peng ◽  
Jiali Wang ◽  
Yang Xiang
Keyword(s):  
Signal Transduction ◽  
Tumor Marker ◽  
Tumor Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Vital Role ◽  
Structure And Function ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
Integrin Β4 ◽  
And Function

Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial–mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.

scholarly journals Mechanotransduction in tumor progression: The dark side of the force

2018 ◽  
Vol 217 (5) ◽  
pp. 1571-1587 ◽  
Author(s):  
Florence Broders-Bondon ◽  
Thanh Huong Nguyen Ho-Bouldoires ◽  
Maria-Elena Fernandez-Sanchez ◽  
Emmanuel Farge
Keyword(s):  
Cell Cycle ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Hydrodynamic Pressure ◽  
Dark Side ◽  
Mesenchymal Transition ◽  
Biochemical Pathways ◽  
Protein Conformational Changes ◽  
Tumor Tissues

Cancer has been characterized as a genetic disease, associated with mutations that cause pathological alterations of the cell cycle, adhesion, or invasive motility. Recently, the importance of the anomalous mechanical properties of tumor tissues, which activate tumorigenic biochemical pathways, has become apparent. This mechanical induction in tumors appears to consist of the destabilization of adult tissue homeostasis as a result of the reactivation of embryonic developmental mechanosensitive pathways in response to pathological mechanical strains. These strains occur in many forms, for example, hypervascularization in late tumors leads to high static hydrodynamic pressure that can promote malignant progression through hypoxia or anomalous interstitial liquid and blood flow. The high stiffness of tumors directly induces the mechanical activation of biochemical pathways enhancing the cell cycle, epithelial–mesenchymal transition, and cell motility. Furthermore, increases in solid-stress pressure associated with cell hyperproliferation activate tumorigenic pathways in the healthy epithelial cells compressed by the neighboring tumor. The underlying molecular mechanisms of the translation of a mechanical signal into a tumor inducing biochemical signal are based on mechanically induced protein conformational changes that activate classical tumorigenic signaling pathways. Understanding these mechanisms will be important for the development of innovative treatments to target such mechanical anomalies in cancer.

scholarly journals Acidic microenvironment modulates ROR1 to promote epithelial-mesenchymal transition and hepatocarcinoma metastasis

2021 ◽  
pp. jcs.255349
Author(s):  
Xia Meng ◽  
Yurui Xu ◽  
Xinghai Ning
Keyword(s):  
Cell Migration ◽  
Tyrosine Kinases ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Orphan Receptor ◽  
High Rate ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Acidic Microenvironment

The tendency of metastasis in hepatocarcinoma results in a high rate of mortality, making it a hot research topic in cancer studies. Although tumor acidic microenvironment has been proved to promote cancer metastasis, its underlying regulatory mechanisms remain poorly defined. Here, we found that acidic conditions significantly enhanced cell migration and invasion ability in hepatocellular carcinoma, and the expression of receptor tyrosine kinases-like orphan receptor 1 (ROR1) was distinctly upregulated in acid-treated cells. In addition, siRNA knockdown of ROR1 could effectively inhibit acid-induced cell migration, invasion and epithelial-mesenchymal transition (EMT). Importantly, neutralization of acidic environment with NaHCO3 could downregulate acid-stimulated ROR1 expression, thereby retarding cell metastatic potential. Especially, the formation of metastatic nodules was significantly increased after intrapulmonary injection of acid stimulated cancer cells, which were inhibited by pretreating with NaHCO3. In summary, we reveal that tumor acidic microenvironment modulates ROR1 expression to promote tumor metastasis, which provides not only a better understanding of molecular mechanism related to metastasis, but a promising target for tumor management.

scholarly journals INFLUENCE OF CHRONIC NEUROGENIC PAIN ON DYNAMICS OF ENDOTHELIN-1 LEVEL AND COMPONENTS OF NO-SYSTEM DURING MELANOMA B16/F10 GROWTH

2018 ◽  
Vol 23 (3-6) ◽  
pp. 180-188
Author(s):  
O. I Kit ◽  
I. M Kotieva ◽  
E. M Frantsiyants ◽  
Ekaterina I. Surikova ◽  
I. V Kaplieva ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Tumor Growth ◽  
Tumor Antigens ◽  
Epithelial Mesenchymal Transition ◽  
Neurogenic Pain ◽  
Mesenchymal Transition ◽  
Endothelin 1 ◽  
Tumor Tissues ◽  
Group 2 ◽  
Skin Conditions

Chronic neurogenic pain is a pathogenic factor triggering mechanisms of homeostasis disfunction. As chronic neurogenic pain has been found to affect the biological features of B16/F10 melanoma, the purpose of the study was to determine the levels of endothelin-1 and components of the NO-system in mice during the growth of transplantable B16/F10 melanoma with chronic pain. Methods. The study included 64 female mice. B16/F10 melanoma was transplanted under the skin of the back to animals of the main group 2 weeks after the sciatic nerve ligation. Levels of endothelin-1, NOS-2, NOS-3, L-arginine, citrulline, total nitrite, nitrotyrosine and ADMA were determined by ELISA in the intact skin and in tumor tissues. Results. The dynamics of the studied parameters in tumor growth with and without chronic pain was different. Increased levels of endothelin-1 in the skin and in tumor tissues, stably elevated levels of NO-synthases in the tumor and stably elevated ADMA levels with their decrease by week 3 of the growth were observed in the tumor growth with pain. Conclusions. Chronic pain can contribute to the development of the immune tolerance to tumor antigens in the skin. Conditions are formed that both facilitate the survival of tumor cells and contribute to the further development of melanoma. The dynamics of activity of endothelin-1 and NO systems can promote stimulation of the epithelial-mesenchymal transition, enhance tumor invasion and hemangio- and lymphangiogenesis. Changes in the ADMA inhibitor levels in the tumor growth with chronic pain may indicate a more subtle control of the NO level providing increased melanoma invasiveness.

scholarly journals Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

2019 ◽  
Author(s):  
Kimberley C. Agbo ◽  
Jessie Z. Huang ◽  
Amr M. Ghaleb ◽  
Jennie L. Williams ◽  
Kenneth R. Shroyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Differentiated Cells ◽  
Colorectal Cancer Resection ◽  
Klf4 Expression ◽  
Tumor Tissues ◽  
Multistep Process ◽  
Epithelial Marker

AbstractColorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examines the relationship between KLF4 and markers of EMT in CRC.MethodsImmunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer.ResultsWe found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, β-catenin, claudin-1, N-cadherin, and vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, β-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin.ConclusionThese findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

scholarly journals Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Chang-Mei Weng ◽  
Qing Li ◽  
Kui-Jun Chen ◽  
Cheng-Xiong Xu ◽  
Meng-Sheng Deng ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
A549 Cells ◽  
Akt Signaling ◽  
High Rate ◽  
Akt Inhibitor ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial–mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the pulmonary fibrosis inducer bleomycin simultaneously increased the expression of bFGF and TGF-β1 and inhibited epithelial-specific regulatory protein (ESRP1) expression in vivo and in vitro. In addition, in vitro experiments showed that bFGF and TGF-β1 down-regulated the expression of ESRP1 and that silencing ESRP1 promoted EMT in A549 cells. Notably, we determined that bFGF activates PI3K/Akt signaling, and treatment with the PI3K/Akt inhibitor LY294002 inhibited bleomycin-induced cell morphology changes and EMT. In addition, the effects of LY294002 on bleomycin-induced EMT were inhibited by ESRP1 silencing in A549 cells. Taken together, these findings suggest that bleomycin induced EMT through down-regulating ESRP1 by simultaneously increasing bFGF and TGF-β1 in pulmonary fibrosis. Additionally, our findings indicated that bFGF inhibits ESRP1 by activating PI3K/Akt signaling.

scholarly journals Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p

2018 ◽  
Vol 33 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Qiang Meng ◽  
Bao-Ying Yang ◽  
Bei Liu ◽  
Ji-Xue Yang ◽  
Yang Sun
Keyword(s):  
Cell Proliferation ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Primary Brain Tumor ◽  
Normal Brain ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Glioma Cell Proliferation ◽  
Long Non Coding Rna

Introduction: Glioma is the most common primary brain tumor. The small nucleolar RNA host gene (SNHG) SNHG6 is a potential oncogene in the development of several types of cancers. Methods: In this study, we investigated the functional role of long non-coding RNA (lncRNA) SNHG6 in the malignancy of glioma in cell lines and transplanted nude mice. Results: We found that the expression of lncRNA SNHG6 was higher in glioma tissues and cells than in normal brain tissues and cells. The expression of lncRNA SNHG6 was positively correlated with the malignancy and poor prognosis of glioma patients. microRNA (miR)-101-3p expression was decreased in glioma tissues and cells and was negatively correlated with the malignancy and poor prognosis of glioma patients. In glioma tissues, the expression of lncRNA SNHG6 was negatively correlated with the expression of miR-101-3p. SNHG6 contained a binding site of miR-101-3p. Knockdown of SNHG6 expression resulted in a significant increase of miR-101-3p expression. miR-101-3p mimic markedly decreased the luciferase activity of SNHG6. Knockdown of SNHG6 inhibited glioma cell proliferation, migration, and epithelial-mesenchymal transition (EMT), and increased apoptosis. miR-101-3p mimic enhanced knockdown of SNHG6-induced inhibition of cell proliferation, migration, and EMT, and an increase of apoptosis. Anti-miR-101-3p reversed the the effects of si-SNHG6 on cell malignancy. Knockdown of SNHG6 remarkably reduced the increase of tumor volumes in xenograft mouse models. In tumor tissues, knockdown of SNHG6 increased the expression of miR-101-3p and reduced EMT biomarker expression. Conclusions: Our study provides novel insights into the functions of lncRNA SNHG6/miR-101-3p axis in the tumorigenesis of glioma.

scholarly journals LncRNA MIAT as a Stemness-Associated Transcript Regulates the Proliferation, Migration and Metastasis of Glioma

2021 ◽  
Author(s):  
Farzane Amirmahani ◽  
Malek Hossein Asadi ◽  
Sadeq Vallian
Keyword(s):  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration Ability ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Cycle Arrest ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Micro Rnas ◽  
Induced Apoptosis

Abstract Purpose: Glioma is the most prevalent category of brain tumors with cancer stem cells. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA), with altered expression in different diseases and cancers. The purpose of this study was to evaluate the functional role of lncRNA MIAT in glioma.Methods: In this study, lncRNA MIAT expression was evaluated in the TCGA database in common cancers and glioma specimens. The expression of lncRNA MIAT was knocked down by the RNA interference method, and its effects on the characteristics of two glioma cancer cell lines, A172 and U-87MG, were investigated. Results: The findings of the bioinformatics analysis showed an increase in the expression level of lncRNA MIAT in 12 common cancers. The expression of lncRNA MIAT was much greater in glioma tumor tissues compared to other ones. Knocking-down of lncRNA MIAT led to the reduction of proliferation of glioma cancer cells followed by cell cycle arrest at G1 phase. Furthermore, the inhibition of expression of lncRNA MIAT significantly induced apoptosis, senescence and autophagy, but limited the migration ability and Epithelial-Mesenchymal-Transition (EMT) of cancer cells. Moreover, knocking-down of lncRNA MIAT reduced the expression of stemness factors including Oct4, Sox2, and Nanog. This resulted in the upregulation of their downstream miRNAs (micro RNAs), let-7a-5p and miR-29b-3p. Conclusion: Altogether, our findings showed that lncRNA MIAT could control proliferation, migration and metastasis of glioma cells by regulating the Nanog/ Sox2 / MAP1LC3B2/ let-7a-5p / miR-29b-3p axis. These observations proposed that lncRNA MIAT could be considered as a new oncogene in glioma.

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