scholarly journals Generation of Two Paclitaxel-Resistant High-Grade Serous Carcinoma Cell Lines With Increased Expression of P-Glycoprotein

2021 ◽  
Vol 11 ◽  
Author(s):  
Mariana Nunes ◽  
Patrícia M. A. Silva ◽  
Ricardo Coelho ◽  
Carla Pinto ◽  
Albina Resende ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Serous Carcinoma ◽  
Drug Efflux ◽  
High Grade ◽  
Intrinsic Resistance ◽  
Paclitaxel Resistance ◽  
Carcinoma Cell Lines ◽  
P Glycoprotein

Debulking surgery followed by chemotherapy are the standard of care for high-grade serous carcinoma. After an initial good response to treatment, the majority of patients relapse with a chemoresistant profile, leading to a poor overall survival. Chemotherapy regimens used in high-grade serous carcinomas are based in a combination of classical chemotherapeutic drugs, namely, Carboplatin and Paclitaxel. The mechanisms underlying drug resistance and new drug discovery are crucial to improve patients’ survival. To uncover the molecular mechanisms of chemoresistance and test drugs capable of overcoming this resistant profile, it is fundamental to use good cellular models capable of mimicking the chemoresistant disease. Herein, we established two high-grade serous carcinoma cell lines with intrinsic resistance to Carboplatin and induced Paclitaxel resistance (OVCAR8 PTX R C and OVCAR8 PTX R P) derived from the OVCAR8 cell line. These two chemoresistant cell line variants acquired an enhanced resistance to Paclitaxel-induced cell death by increasing the drug efflux capacity, and this resistance was stable in long-term culture and following freeze/thaw cycles. The mechanism underlying Paclitaxel resistance resides in a significant increase in P-glycoprotein expression and, when this drug efflux pump was blocked with Verapamil, cells re-acquired Paclitaxel sensitivity. We generated two high-grade serous carcinoma cell lines, with a double-chemoresistant (Carboplatin and Paclitaxel) phenotype that mimics the majority of tumor recurrences in ovarian cancer context. This robust tool is suitable for preliminary drug testing towards the development of therapeutic strategies to overcome chemoresistance.

scholarly journals Identification of ovarian high-grade serous carcinoma cell lines that show estrogen-sensitive growth as xenografts in immunocompromised mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexis De Haven Brandon ◽  
Gary Box ◽  
Albert Hallsworth ◽  
William Court ◽  
Nicoll Matthews ◽  
...  
Keyword(s):  
Cell Lines ◽  
Carcinoma Cell ◽  
Serous Carcinoma ◽  
High Grade ◽  
Carcinoma Cell Lines ◽  
Immunocompromised Mice

Establishment and characterization of 7 ovarian carcinoma cell lines and one granulosa tumor cell line: Growth features and cytogenetics

1993 ◽  
Vol 53 (4) ◽  
pp. 613-620 ◽  
Author(s):  
Cornelia A. M. van den Berg-Bakker ◽  
Anne Hagemeijer ◽  
Elsa M. Franken-Postma ◽  
Vincent T. H. B. M. Smit ◽  
Peter J. K. Kuppen ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Ovarian Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Tumor Cell Line ◽  
Carcinoma Cell Lines ◽  
Growth Features

Abstract 5876: Exploratory testing of PM060184 compound in high-grade serous ovarian carcinoma cell lines

2018 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
Alejandro Gallego ◽  
María Miguel-Martín ◽  
Roberto Crespo ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
High Grade ◽  
Carcinoma Cell Lines ◽  
Serous Ovarian Carcinoma ◽  
Exploratory Testing

scholarly journals Localization of MOC-1 cell surface antigen in small-cell lung carcinoma cell lines: an immunohistochemical and immunoelectron microscopic study.

1993 ◽  
Vol 41 (9) ◽  
pp. 1303-1310 ◽  
Author(s):  
V Speirs ◽  
S Eich-Bender ◽  
C R Youngson ◽  
E Cutz
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Western Blot ◽  
Cell Line ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Small Cell ◽  
Cell Contact ◽  
Positive Staining ◽  
Carcinoma Cell Lines

Expression of cell surface antigens of the neural cell adhesion molecule (N-CAM) class was recently shown to be shared by both fetal and neoplastic neuroendocrine cells, including those of the lung. We investigated the expression and localization of MOC-1 antigen on small-cell (neuroendocrine) lung carcinoma cell lines with immunohistochemical methods at the light (LM) and electron microscopy (EM) level and by Western blot. At LM level, using monoclonal antibody (MAb) MOC-1 with the ABC method and immunofluorescence, positive staining was observed on surfaces of cells from all tumor lines examined. Strongest immunostaining was found on cell surfaces of pulmonary small-cell carcinoma-derived cell line NCI-H69 with the majority of cells showing positive staining. An adherent variant of NCI-H69 cell line, H69V, exhibited positive staining in about 60% of cells, whereas only occasional cells of NCI-H727 cell line derived from pulmonary carcinoid tumor were positive for MOC-1 antigen. Western blot analysis confirmed these findings, showing a strong MOC-1-specific band in cell extracts of NCI-H69, with weaker band densities for H69V and NCI-H727. Immunoelectron microscopy (IEM) revealed that MOC-1 was not uniformly distributed on the outer surface of plasma membrane; immunogold particles appeared concentrated in areas of thick cell surface "fuzz" coating, surface microvilli, and in areas of cell-cell contact. In some cells, areas of plasma membrane invaginations and a few intracytoplasmic vesicles were also labeled, suggesting endocytosis. Surface labeling for SEM confirmed the finding of more dense labeling over the microvilli, cell membrane folds, and in areas of cell-cell contact. The cell lines derived from pulmonary neuroendocrine cell tumors can provide a useful model to study the role and function of neural adhesion molecules in pulmonary neoplasia and during lung development.

Differential anthracycline sensitivity in two related human colon carcinoma cell lines expressing similar levels of P-glycoprotein

2001 ◽  
Vol 165 (1) ◽  
pp. 111-116 ◽  
Author(s):  
Alejandra L Boquete ◽  
Laura Vargas Roig ◽  
Gustavo A López ◽  
Rajiv Gude ◽  
M.Mercedes Binda ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Human Colon ◽  
Human Colon Carcinoma Cell ◽  
Carcinoma Cell Lines ◽  
Human Colon Carcinoma ◽  
P Glycoprotein

scholarly journals Matrix metalloproteinases (MMP) - MMP-1,-2,-9 and its endogenous activity regulators in transformed by E7 oncogene HPV16 and HPV18 cervical carcinoma cell lines

2013 ◽  
Vol 59 (5) ◽  
pp. 530-540 ◽  
Author(s):  
O.S. Ryzhakova ◽  
N.I. Solovyeva
Keyword(s):  
Matrix Metalloproteinases ◽  
Cell Line ◽  
Cell Lines ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
Control Level ◽  
Transformed Cells ◽  
Collagenolytic Activity ◽  
Carcinoma Cell Lines ◽  
Hpv 18

Matrix metalloproteinases (MMP) play a key role in development of tumor invasion and metestasis. The purpose of the work is the elucidation of peculiarities of expression of MMP-1, MMP-2, MMP-9 and their activity regulators: plasminogen activator uPA and tissue inhibitors of MMPs - TIMP-1 and TIMP-2 in human cell lines of squoamous cell carcinoma (SCC). Comparative study of MMPs’ expression was carried out on cell lines SCC which differed in HPV types (HPV-16 and HPV-18): SiHa, Caski – НРV16, Hela, С4-1 – HPV18). As a control, the С33А line was used where HPV copies were absent. The human papilloma viruses (HPV) of high risk – HPV-16, HPV-18, as etiological factors of initiation of cervical cancer, are most widespread and most aggressive among oncogenic HPVs. Study of MMP expression involved estimation of expression of mRNA using the RT-PCR method and determination of collagenolytic activity by hydrolysis of fluorogenic type 1 collagen and also by the zymography method. It was shown that: 1. In both types of cell lines, the MMP-1 expression was essentially increased (2 to 8 times), and in HPV18 lines it was most expressed. The exception was made by the SiHa line in which the decrease of expression of this enzyme was observed. MMP-2 expression was at the control level in both types of cell lines. 2. Expression of inhibitors generally was at the control level. The only exception was the C4-1 line where the expression of TIMP-1 and TIMP-2 was increased in 1,7 and 2,6 times accordingly. Expression of uPA was increased 2 to 4,5 times in all cell lines except Siha where was lowered to 20%. 3. Collagenolytic activity in the Caski and Hela cell line was 2-3 times higher that it was in control, while the activity in the SiHa cell line was compatible with that in the control. Research of gelatinolytic activity also as well as the data on an expression мРНК has revealed only presence ММП-2, but not ММП-9 in all cervical carcinoma cell lines. The data obtained provide evidence for a significant disturbance in transformed cells of enzyme/inhibitor/activator ratio – which occurs, for the most part, at the cost of elevated expression of MMP-1 and its activator whereas the expression of MMP-2 and inhibitors remains virtually unchanged, which leads to the increase of the destructive potential of transformed cells.

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