Application of sequential cyclic compression on cancer cells in a flexible microdevice

Mechanical forces shape physiological structure and function within cell and tissue microenvironments, during which cells strive to restore their shape or develop an adaptive mechanism to maintain cell integrity depending on strength and type of the mechanical loading. While some cells are shown to experience permanent plastic deformation after a repetitive mechanical tensile loading and unloading, the impact of such repetitive compression on plastic deformation of cells is yet to be discovered. As such, the ability to apply cyclic compression is crucial for any experimental setup aimed at the study of mechanical compression taking place in cell and tissue microenvironments. Here, the capability of our microfluidic compression platform to aid in the observation of the sequential cyclic compression of live cell actin is illustrated using SKOV-3 ovarian cancer cells. Live imaging of the actin cytoskeleton dynamics of the compressed cells was performed for the applied varying pressures in ascending order during cell compression. Additionally, recovery of the compressed cells was investigated by capturing actin cytoskeleton and nuclei profiles of the cells at zero time and 24 h-recovery after compression in end point assays. This was performed for a range of mild pressures within the physiological range. The extent of recovery of the compressed cells can give insights into the plasticity of the cancer cells by imaging cell membrane bulges and actin cytoskeleton and measuring the shape descriptors of cell nuclei. As demonstrated in this work, the developed platform can control the strength and duration of cyclic compression, while enabling the observation of morphological and cytoskeletal and nuclear changes in cells, thus providing a powerful new tool for the study of mechanobiological processes in cancer and cell biology.

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Adenosine Analogues as Opposite Modulators of the Cisplatin Resistance of Ovarian Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190118113201 ◽

2019 ◽

Vol 19 (4) ◽

pp. 473-486 ◽

Cited By ~ 1

Author(s):

Katarzyna Bednarska-Szczepaniak ◽

Damian Krzyżanowski ◽

Magdalena Klink ◽

Marek Nowak

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Biology ◽

Immune Cell ◽

Immunosuppressive Agents ◽

Cell Activity ◽

Ovarian Cancer Cells ◽

Adenosine Analogues

Background: Adenosine released by cancer cells in high amounts in the tumour microenvironment is one of the main immunosuppressive agents responsible for the escape of cancer cells from immunological control. Blocking adenosine receptors with adenosine analogues and restoring immune cell activity is one of the methods considered to increase the effectiveness of anticancer therapy. However, their direct effects on cancer cell biology remain unclear. Here, we determined the effect of adenosine analogues on the response of cisplatinsensitive and cisplatin-resistant ovarian cancer cells to cisplatin treatment. Methods: The effects of PSB 36, DPCPX, SCH58261, ZM 241385, PSB603 and PSB 36 on cisplatin cytotoxicity were determined against A2780 and A2780cis cell lines. Quantification of the synergism/ antagonism of the compounds cytotoxicity was performed and their effects on the cell cycle, apoptosis/necrosis events and cisplatin incorporation in cancer cells were determined. Results: PSB 36, an A1 receptor antagonist, sensitized cisplatin-resistant ovarian cancer cells to cisplatin from low to high micromolar concentrations. In contrast to PSB 36, the A2AR antagonist ZM 241385 had the opposite effect and reduced the influence of cisplatin on cancer cells, increasing their resistance to cisplatin cytotoxicity, decreasing cisplatin uptake, inhibiting cisplatin-induced cell cycle arrest, and partly restoring mitochondrial and plasma membrane potentials that were disturbed by cisplatin. Conclusion: Adenosine analogues can modulate considerable sensitivity to cisplatin of ovarian cancer cells resistant to cisplatin. The possible direct beneficial or adverse effects of adenosine analogues on cancer cell biology should be considered in the context of supportive chemotherapy for ovarian cancer.

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Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Journal of Clinical Medicine ◽

10.3390/jcm9041185 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1185 ◽

Cited By ~ 3

Author(s):

Martha Baydoun ◽

Olivier Moralès ◽

Céline Frochot ◽

Colombeau Ludovic ◽

Bertrand Leroux ◽

...

Keyword(s):

Ovarian Cancer ◽

Immune Response ◽

Photodynamic Therapy ◽

Cancer Cells ◽

Tumor Cells ◽

Extracellular Vesicles ◽

Immune Cells ◽

Surgical Techniques ◽

Ovarian Cancer Cells ◽

The Impact

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

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TCTP Silencing in Ovarian Cancer Cells Results in Actin Cytoskeleton Remodeling and Motility Increase

Journal of Analytical Oncology ◽

10.6000/1927-7229.2015.04.04.1 ◽

2015 ◽

Vol 4 (4) ◽

pp. 122-131 ◽

Cited By ~ 1

Author(s):

Malgorzata Kloc ◽

◽

Yianzhu Liu ◽

Li Zhang ◽

Neelam Tejpal ◽

...

Keyword(s):

Ovarian Cancer ◽

Actin Cytoskeleton ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Cytoskeleton Remodeling

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Impact of LMWH and Specific Factor Xa Inhibitors, Apixaban and Fondaparinux, on Cancer Cell Biology and Procoagulant Properties of Cancer Microenvironment

Blood ◽

10.1182/blood-2021-146456 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2136-2136

Author(s):

Huong Chi Mai Tran ◽

Rania Amrane ◽

Elisabeth Mbemba ◽

Michele Sabbah ◽

Ismail Elalamy ◽

...

Keyword(s):

Gene Expression ◽

Pancreatic Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Biology ◽

Thrombin Generation ◽

Antithrombotic Agents ◽

Pancreatic Cancer Cells ◽

The Impact

Abstract Background Cancer patients with venous thromboembolism (VTE) or at risk of VTE are treated with antithrombotic agents. Cancer cells express procoagulant properties and induce hypercoagulability in the microenvironment, that could impact the efficiency of the antithrombotic agents. Aims In the present study, we investigated the interaction between antithrombotic agents with pancreatic cancer cells, as well as with their microenvironment. The impact of apixaban, fondaparinux, enoxaparin and tinzaparin on the procoagulant properties of pancreatic cancer cells BXPC3 was examinated. Reciprocally, we also investigated the impact of BXPC3 on the potency of these antithrombotic agents. Methods BXPC3 cells (400 cells/μl) were exposed for 48 hours to apixaban (2 µg/ml), fondaparinux (2 µg/ml), enoxaparin, tinzaparin (2 anti-Xa IU/ml) or NaCL (control). Then, conditioned media (CM) and BXPC3 cells were harvested, separated and put in contact with normal platelet-poor plasma (PPP). Subsequently, thrombin generation (TG) was assessed using Thrombogram-Thrombinoscope® assay (Diagnostica Stago). Cells' viability was also assessed with the MTT assay. Gene expression for Tissue Factor (TF), Vascular Endothelial Growth Factor (VEGF), Thrombospondin 1 (THSB1) was assessed with RT-qPCR at the cells exposed or not to the antithrombotic agents. Expression of TF protein and activity of cancer cells was assessed using ELISA method. Residual anti-Xa activity in CM was measured using specific amidolytic assays for each antithrombotic agent. Results Apixaban, fondaparinux, enoxaparin, and tinzaparin significantly reduced cell viability by 25%, 12%, 14%, and 11% respectively. In the control experiment non treated BXPC3 cells enhanced TG. Pre-treatment of BXPC3 with the antithrombotic agents did not significantly modify their capacity to trigger and enhance TG. Among the studied agents only apixaban resulted in significant decrease of TF mRNA expression. However, protein expression of TF was not significantly modified by any of the antithrombotic agents. VEGF's mRNA expression was significantly decreased by fondaparinux and enoxaparin. THBS1's mRNA expression was significantly increased by apixaban. The concentrations of the anti-Xa activity of fondaparinux, enoxaparin and tinzaparin in the CM obtained at 48h after exposure of cells were reduced by 27%, 48% and 26% respectively as compared to those initially added in the culture medium. In contrast, the concentration of apixaban in the CM did not significantly change. The CM obtained by cells exposed to apixaban, fondaparinux, enoxaparin and tinzaparin inhibited TG by 70%, 30%, 40% and 90% respectively. Conclusion. Antithrombotic agents reduced the viability of BXPC3 cells. Among the studied agents, apixaban had the most pronounced effect on cells' viability. The antithrombotic agents had a potential downregulating effect on the proangiogenetic properties of BXPC3 via the decrease of VEGF gene expression (fondaparinux and enoxaparin) and enhancement of THBS1 gene expression (apixaban). Nevertheless, preincubation of BXPC3 with the antithrombotic agents did not alter the expression of TF protein and their effect on thrombin generation. Moreover, BXPCE exerted a "degradation" effect on LMWH and fondaparinux. Apixaban appeared to escape from this effect of the cancer cells. A significant inhibitory effect on thrombin generation was exerted by the residual concentrations of the antithrombotic agents in the microenvironment of cancer cells. The ensemble of these data highlight for the first time that the presence of antithrombotic agents in cancer cell microenvironment alters the biology of cancer cells and offer a constant antithrombotic effect in the microenvironment. Disclosures No relevant conflicts of interest to declare.

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Carboplatin-induced Senescence in Ovarian Cancer Cells Is Reversed Through EGFR and NF-κB Signaling

10.21203/rs.3.rs-215681/v1 ◽

2021 ◽

Author(s):

Yue Li ◽

Mingxu Fu ◽

Ling Guo ◽

Xiaoxiao Sun ◽

Yuhang Chen ◽

...

Keyword(s):

Ovarian Cancer ◽

Western Blot ◽

Cancer Cells ◽

Blot Analysis ◽

Western Blot Analysis ◽

Cell Counting ◽

Blue Staining ◽

Ovarian Cancer Cells ◽

Positive Staining ◽

The Impact

Abstract Background: Metastases and recurrence of ovarian cancer after surgery and chemotherapy account for most cancer-related deaths, yet the mechanism underlying metastases and recurrence remains poorly understood. Recent evidence demonstrates that although long-lasting cells were considered tumor suppressors, senescent cancer cells, can induce the metastases and recurrence. In this study, we focused on the fate of ovarian cancer cells treated with carboplatin and explored the mechanism underlying ovarian cancer cell recovery from chemotherapy-induced senescence. Methods: SÁ-β-galactosidase staining was used to detect the impact of carboplatin on senescence of ovarian cancer cells. Cell proliferation was determined using direct cell counting, clone formation assay and 3D tumor spheroid formation assay. Lentivirus-mediated transduction was used to silence or upregulate EGFR expression. Quantitative real-time PCR and western blot analysis validated the efficacy of the knockdown or overexpression effect. Immunofluorescence staining and western blot analysis were used to examined the expression of EGFR and NF-KB. Cell death was determined using trypan blue staining assay. Results: Ovarian cancer cells treated by carboplatin exhibit a senescence-like phenotype indicated by SA-β-galactosidase positive staining. Importantly, carboplatin-induced senescence-like phenotype is reversible. In ovarian cancer cells, EGFR positively regulated cells proliferation, decreased carboplatin-induced senescence and upregulated the NF-κB1 protein level. EGFR/NF-κB1 upregulation promoted the recovery of ovarian cancer cells from senescence and chemoresistance to carboplatin. Conclusions: Ovarian cancer cells treated with carboplatin displayed a reversible senescence-like phenotype that could be combined with EGFR or NF-κB1 inhibitors to improve treatment effects.

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Cell biology of the movement of breast cancer cells: Intracellular signalling and the actin cytoskeleton

Cancer Letters ◽

10.1016/j.canlet.2009.02.034 ◽

2009 ◽

Vol 284 (2) ◽

pp. 122-130 ◽

Cited By ~ 103

Author(s):

Ping Jiang ◽

Atsushi Enomoto ◽

Masahide Takahashi

Keyword(s):

Breast Cancer ◽

Actin Cytoskeleton ◽

Cancer Cells ◽

Cell Biology ◽

Breast Cancer Cells ◽

Intracellular Signalling

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miR-552 promotes ovarian cancer progression by regulating PTEN pathway

Journal of Ovarian Research ◽

10.1186/s13048-019-0589-y ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 7

Author(s):

Wenman Zhao ◽

Tao Han ◽

Bao Li ◽

Qianyun Ma ◽

Pinghua Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Malignant Tumors ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Cancer Proliferation ◽

Proliferation And Metastasis ◽

The Impact

Abstract Background Increasing researches have demonstrated the critical functions of MicroRNAs (miRNAs) in the progression of malignant tumors, including ovarian cancer. It was reported that miR-552 was an important oncogene in both breast cancer and colorectal cancer. However, the role of miR-552 in ovarian cancer (OC) remains to be elucidated. Methods RT-PCR and western blot analysis were used to detect the expression of miR-552 and PTEN. The impact of miR-552 on ovarian cancer proliferation and metastasis was investigated in vitro. The prognostic value of miR-552 was evaluated using the online bioinformatics tool Kaplan-Meier plotter. Results In the present study, we for first found that miR-552 was upregulated in ovarian cancer, especially in metastatic and recurrence ovarian cancer. Forced miR-552 expression promotes the growth and metastasis of ovarian cancer cells. Consistently, miR-552 interference inhibits the proliferation and metastasis of ovarian cancer cells. Mechanically, bioinformatics and luciferase reporter analysis identified Phosphatase and tension homolog (PTEN) as a direct target of miR-552. miR-552 downregulated the PTEN mRNA and protein expression in ovarian cancer cells. Furthermore, the PTEN siRNA abolishes the discrepancy of growth and metastasis capacity between miR-552 mimic ovarian cells and control cells. More importantly, upregulation of miR-552 predicts the poor prognosis of ovarian cancer patients. Conclusion Our findings revealed that miR-552 could promote ovarian cancer cells progression by targeting PTEN signaling and might therefore be useful to predict patient prognosis.

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p70 S6 kinase in the control of actin cytoskeleton dynamics and directed migration of ovarian cancer cells

Oncogene ◽

10.1038/onc.2010.615 ◽

2011 ◽

Vol 30 (21) ◽

pp. 2420-2432 ◽

Cited By ~ 67

Author(s):

C K M Ip ◽

A N Y Cheung ◽

H Y S Ngan ◽

A S T Wong

Keyword(s):

Ovarian Cancer ◽

Actin Cytoskeleton ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

S6 Kinase ◽

P70 S6 Kinase ◽

Directed Migration ◽

Cytoskeleton Dynamics

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Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1

10.21203/rs.3.rs-20826/v2 ◽

2020 ◽

Author(s):

Chun Hua Liu ◽

Xue Ning Jing ◽

Xiao Lan Liu ◽

Shan Yong Qin ◽

Min Wei Liu ◽

...

Keyword(s):

Ovarian Cancer ◽

Ovarian Carcinoma ◽

Cancer Cells ◽

Carcinoma Cells ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Skov3 Cell ◽

Ovarian Carcinoma Cells ◽

The Impact

Abstract BackgroundMicroRNAs (miRNAs) play crucial functions in the progression of ovarian cancer. MicroRNA-27b-5p (miR-27b-5p) has been identified as a cancer-associated miRNA. Nevertheless, the expression profile of miR-27b-5p and its functions in ovarian cancer are unexplored.MethodsqRT-PCR and western blot analysis were used to detect the levels of miR-27b-5p and C-X-C motif chemokine ligand 1 (CXCL1). The impact of miR-27b-5p on ovarian cancer cells proliferation, migration and invasion in vitro were investigated using Cell Counting Kit-8 (CCK8), wound healing and Transwell, respectively. The expression of matrix metalloprotein-2/9 (MMP-2/9) were measured using immunofluorescence staining. Bioinformatics and luciferase reporter analysis were used to predict the target of miR-27b-5p. The growth of ovarian cancer cells in vivo was evaluated using transplanted tumor model.ResultsHere, we demonstrated that miR-27b-5p was downregulated in ovarian carcinoma cells and clinical specimens. Higher expression of miR-27b-5p was associated with an unfavorable overall survival in patients with ovarian cancer. Upregulation of miR-27b-5p decreased the viability, migration ability and invasion capacity of SKOV3 and OVCAR3 cell. MiR-27b-5p also inhibited the growth of SKOV3 cell in nude mice. Additionally, we verified that CXCL1 was a target of miR-27b-5p in ovarian carcinoma cells. Restoring the expression of CXCL1 abolished the inhibitory impacts of miR-27b-5p in ovarian cancer carcinoma cells.ConclusionThis research revealed that miR-27b-5p restrained the progression of ovarian carcinoma possibly via targeting CXCL1.

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