دورية أكاديمية
Proteomic analysis of gemcitabine-resistant pancreatic cancer cells reveals that microtubule-associated protein 2 upregulation associates with taxane treatment
| العنوان: | Proteomic analysis of gemcitabine-resistant pancreatic cancer cells reveals that microtubule-associated protein 2 upregulation associates with taxane treatment |
|---|---|
| المؤلفون: | Tessa Ya Sung Le Large, Btissame El Hassouni, Niccola Funel, Bart Kok, Sander R. Piersma, Thang V. Pham, Kenneth P. Olive, Geert Kazemier, Hanneke W.M. van Laarhoven, Connie R. Jimenez, Maarten F. Bijlsma, Elisa Giovannetti |
| المصدر: | Therapeutic Advances in Medical Oncology, Vol 11 (2019) |
| بيانات النشر: | SAGE Publishing, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Background: Chemoresistance hampers the treatment of patients suffering from pancreatic ductal adenocarcinoma (PDAC). Here we aimed to evaluate the (phospho)proteome of gemcitabine-sensitive and gemcitabine-resistant PDAC cells to identify novel therapeutic targets and predictive biomarkers. Methods: The oncogenic capabilities of gemcitabine-sensitive and resistant PDAC cells were evaluated in vitro and in vivo . Cultured cells were analyzed by label-free proteomics. Differential proteins and phosphopeptides were evaluated by gene ontology and for their predictive or prognostic biomarker potential with immunohistochemistry of tissue microarrays. Results: Gemcitabine-resistant cells had increased potential to induce xenograft tumours ( p value < 0.001). Differential analyses showed that proteins associated with gemcitabine resistance are correlated with microtubule regulation. Indeed, gemcitabine-resistant cells displayed an increased sensitivity for paclitaxel in vitro ( p < 0.001) and nab-paclitaxel had a strong anti-tumour efficacy in vivo . Microtubule-associated protein 2 (MAP2) was found to be highly upregulated ( p = 0.002, fold change = 10) and phosphorylated in these resistant cells. Expression of MAP2 was correlated with a poorer overall survival in patients treated with gemcitabine in the palliative ( p = 0.037) and adjuvant setting ( p = 0.014). Conclusions: These data show an explanation as to why the combination of gemcitabine with nab-paclitaxel is effective in PDAC patients. The identified gemcitabine-resistance marker, MAP2, emerged as a novel prognostic marker in PDAC patients treated with gemcitabine and warrants further clinical investigation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1758-8359 17588359 |
| العلاقة: | https://doaj.org/toc/1758-8359Test |
| DOI: | 10.1177/1758835919841233 |
| الوصول الحر: | https://doaj.org/article/f08fde4d92bb4c4db062c946b643bd68Test |
| رقم الانضمام: | edsdoj.f08fde4d92bb4c4db062c946b643bd68 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17588359 |
|---|---|
| DOI: | 10.1177/1758835919841233 |