The role of tumor acidification in aggressiveness, cell dissemination and treatment resistance of oral squamous cell carcinoma

Prunes, Bianca De Bem; Nunes, Júlia Silveira; Silva, Viviane Palmeira da; Laureano, Natalia Koerich; Gonçalves, Douglas Rodrigues; Machado, Ian Santana; Barbosa, Sílvia; Lamers, Marcelo Lazzaron; Rados, Pantelis Varvaki; Kurth, Ina; Heß, Jochen; Jou, Adriana; Visioli, Fernanda

doi:10.1016/j.lfs.2021.120163

Cited by 14 publications

(2 citation statements)

References 90 publications

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“…Due to the expanding evidence that miRNAs are associated with chemotherapy resistance, the overall goal of this project was to evaluate both oral cancer resistance and miRNA expression to determine whether significant relationships could be identified. The results of this study clearly demonstrated at least two oral cancer cell lines (SCC9 and SCC25) with significant resistance to all three main chemotherapies (Cisplatin, 5-FU and Taxol), confirming recent observations made in other studies of chemotherapy resistance [ 29 , 30 , 31 , 32 ]. These data contribute to a body of important research that seeks to identify model systems for evaluating the mechanisms responsible for chemotherapy resistance among oral cancers [ 33 ].…”

Section: Discussionsupporting

confidence: 90%

Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines

Huni

Cheung²,

Sullivan³

et al. 2023

IJMS

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Recent advances have suggested that non-coding miRNAs (such as miR-21, miR-27, miR-145, miR-155, miR-365, miR-375 and miR-494) may be involved in multiple aspects of oral cancer chemotherapeutic responsiveness. This study evaluated whether these specific miRNAs are correlated with oral cancer responsiveness to chemotherapies, including Paclitaxel, Cisplatin and Fluorouracil (5FU). Commercially available and well-characterized oral squamous cell carcinoma cell lines (SCC4, SCC9, SCC15, SCC25 and CAL27) revealed differing resistance and chemosensitivity to these agents—with SCC9 and SCC25 demonstrating the most resistance to all chemotherapeutic agents. SCC9 and SCC25 were also the only cell lines that expressed miR-375, and were the only cell lines that did not express miR-27. In addition, the expression of miR-375 was associated with the upregulation of Rearranged L-myc fusion (RLF) and the downregulation of Centriolar protein B (POC1), whereas lack of miR-27 expression was associated with Nucleophosmin 1 (NPM1) expression. These data have revealed important regulatory pathways and mechanisms associated with oral cancer proliferation and resistance that must be explored in future studies of potential therapeutic interventions.

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Section: Discussionsupporting

confidence: 90%

Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines

Huni

Cheung²,

Sullivan³

et al. 2023

IJMS

View full text Add to dashboard Cite

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“…This metabolic switch leads to protons and lactate extrusion, which, in the absence of effective lymphatic support, accumulate and contribute to extracellular acidosis [ 20 ]. The extracellular pH of melanoma lesions ranges between 6.4/6.6 to 7.0/7.3 [ 11 , 12 ], and acidosis is associated with a poorer prognosis and aggressiveness in many different types of cancer [ 21 , 22 , 23 , 24 , 25 , 26 ]. Considering the ability of acidosis to reconvert tumor cells toward an aggressive phenotype, we focused our study on the possible gender disparity of ERβ expression on acidic melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Acidosis Differentially Regulates Estrogen Receptor β-Dependent EMT Reprogramming in Female and Male Melanoma Cells

Peppicelli

Ruzzolini

Lulli

et al. 2022

IJMS

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Clinical outcomes of melanoma patients pointed out a gender disparity that supports a correlation between sex hormone activity on estrogen receptors (ER) and melanoma development and progression. Here, we found that the epithelial-to-mesenchymal transition (EMT) of melanoma cells induced by extracellular acidosis, which is a crucial hallmark of solid cancers, correlates with the expression of ERβ, the most representative ER on melanoma cells. Extracellular acidosis induces an enhanced expression of ERβ in female cells and EMT markers remain unchanged, while extracellular acidosis did not induce the expression of ERβ in male cells and EMT was strongly promoted. An inverse relationship between ERβ expression and EMT markers in melanoma cells of different sex exposed to extracellular acidosis was revealed by two different technical approaches: florescence-activated cell sorting of high ERβ expressing cell subpopulations and ERβ receptor silencing. Finally, we found that ERβ regulates EMT through NF-κB activation. These results demonstrate that extracellular acidosis drives a differential ERβ regulation in male and female melanoma cells and that this gender disparity might open new perspectives for personalized therapeutic approaches.

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Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers

Dorna

Paluszczak

2023

J Cancer Res Clin Oncol

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Purpose Resistance to chemotherapy and radiotherapy is the primary cause of a poor prognosis in oncological patients. Researchers identified many possible mechanisms involved in gaining a therapy-resistant phenotype by cancer cells, including alterations in intracellular drug accumulation, detoxification, and enhanced DNA damage repair. All these features are characteristic of stem cells, making them the major culprit of chemoresistance. This paper reviews the most recent evidence regarding the association between the stemness phenotype and chemoresistance in head and neck cancers. It also investigates the impact of pharmacologically targeting cancer stem cell populations in this subset of malignancies. Methods This narrative review was prepared based on the search of the PubMed database for relevant papers. Results Head and neck cancer cells belonging to the stem cell population are distinguished by the high expression of certain surface proteins (e.g., CD10, CD44, CD133), pluripotency-related transcription factors (SOX2, OCT4, NANOG), and increased activity of aldehyde dehydrogenase (ALDH). Chemotherapy itself increases the percentage of stem-like cells. Importantly, the intratumor heterogeneity of stem cell subpopulations reflects cell plasticity which has great importance for chemoresistance induction. Conclusions Evidence points to the advantage of combining classical chemotherapeutics with stemness modulators thanks to the joint targeting of the bulk of proliferating tumor cells and chemoresistant cancer stem cells, which could cause recurrence.

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The role of tumor acidification in aggressiveness, cell dissemination and treatment resistance of oral squamous cell carcinoma

Cited by 14 publications

References 90 publications

Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines

Chemotherapeutic Drug Resistance Associated with Differential miRNA Expression of miR-375 and miR-27 among Oral Cancer Cell Lines

Extracellular Acidosis Differentially Regulates Estrogen Receptor β-Dependent EMT Reprogramming in Female and Male Melanoma Cells

Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers

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