MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis
| العنوان: | MAL gene overexpression as a marker of high-grade serous ovarian carcinoma stem-like cells that predicts chemoresistance and poor prognosis |
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| المؤلفون: | Francesca Ricci, Maurizio D'Incalci, Antonella Ravaggi, Franco Odicino, Laura Zanotti, Stefano Calza, Germana Tognon, Chiara Romani, Giovanna Damia, Elisabetta Bandiera, Sergio Pecorelli, Enrico Sartori, Renata A. Tassi, Laura Ardighieri, Laura Tassone, Luca Beltrame, Eliana Bignotti, Sergio Marchini, Paola Todeschini |
| المصدر: | BMC Cancer, Vol 17, Iss 1, Pp 1-11 (2017) BMC Cancer |
| بيانات النشر: | BMC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Pathology, Cancer Research, Microarray, Metastasis, 0302 clinical medicine, Ovarian carcinoma, ATP Binding Cassette Transporter, Subfamily G, Member 2, Aged, 80 and over, Ovarian Neoplasms, education.field_of_study, Cancer stem cells, Myelin and Lymphocyte-Associated Proteolipid Proteins, Middle Aged, MAL, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Neoplasm Proteins, Up-Regulation, Gene Expression Regulation, Neoplastic, Serous fluid, Oncology, 030220 oncology & carcinogenesis, Disease Progression, Neoplastic Stem Cells, Female, Stem cell, Chemoresistance, Research Article, Adult, medicine.medical_specialty, Population, Antineoplastic Agents, Context (language use), lcsh:RC254-282, 03 medical and health sciences, Cancer stem cell, Biomarkers, Tumor, medicine, Genetics, Humans, education, Aged, business.industry, Epithelial ovarian cancer, medicine.disease, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, Neoplasms, Cystic, Mucinous, and Serous, business |
| الوصف: | Background The existence of cancer stem cells (CSCs) within a tumor bulk has been demonstrated for many solid tumors including epithelial ovarian carcinoma (EOC). CSCs have been associated to tumor invasion, metastasis and development of chemoresistant recurrences. In this context, we aim to characterize EOC CSCs from the molecular point of view in order to identify potential biomarkers associated with chemoresistance. Methods We isolated a population of cells with stem-like characteristics (OVA-BS4 spheroids) from a primary human EOC cell line under selective conditions. OVA-BS4 spheroids were characterized for drug response by cytotoxicity assays and their molecular profile was investigated by microarray and RT-qPCR. Finally, we performed a gene expression study in a cohort of 74 high-grade serous EOC (HGSOC) patients by RT-qPCR. Results Spheroids exhibited properties of self-renewal and a pronounced expression of well-known stem cell genes. Moreover, they demonstrated greater resistance towards several anticancer drugs compared to parent cell line, consistent with their higher ABCG2 gene expression. From microarray studies MAL (T-cell differentiation protein) emerged as the most up-regulated gene in spheroids, compared to parent cell line. In HGSOC patients, MAL was significantly overexpressed in platinum-resistant compared to platinum-sensitive patients and resulted as an independent prognostic marker of survival. Conclusions This investigation provides an important contribution to the identification of molecular markers of ovarian CSCs and chemoresistance. Successful translation of molecular findings would lead to a better comprehension of the mechanisms triggering chemoresistant recurrences, to the individuation of novel therapeutic targets and to the personalization of treatment regimens. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3334-1) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1471-2407 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09a51c6085dd5068a1e4996bd79d186cTest http://link.springer.com/article/10.1186/s12885-017-3334-1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....09a51c6085dd5068a1e4996bd79d186c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712407 |
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