scholarly journals A mechanical memory of pancreatic cancer cells

2019 ◽  
Author(s):  
Ilaria Carnevale ◽  
Mjriam Capula ◽  
Elisa Giovannetti ◽  
Thomas Schmidt ◽  
Stefano Coppola
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Traction Force ◽  
Long Term Memory ◽  
Mechanical Stimuli ◽  
Mechanical Adaptation ◽  
Pancreatic Cancer Cells ◽  
Mechanical Memory

Cells sense and respond to mechanical stimuli in healthy and pathological conditions. Although the major mechanisms un-derlying cellular mechanotransduction have been described, it remains largely unclear how cells store information on past mechanical cues over time. Such mechanical memory is extremely relevant in the onset of metastasis in which cancer cells migrate through tissues of different stiffness, e.g. from a stiffer tumor microenvironment to softer metastatic sites as commonly occurs for pancreatic cancer. Here, we used micropillar-based traction force microscopy to show that Suit-2.28 pancreatic cancer cells mechanically primed on a stiff matrix exerted higher traction forces even when transferred to a soft secondary matrix, as compared to soft-primed cells. This mechanical memory effect was mediated by the Yes-associated protein (YAP) and the microRNA-21 (miR-21) that are two mechanosensors initially identified as long-term memory keepers in mesenchymal stem cells. Soft-primed cells showed (i) a lower YAP nuclear translocation when transferred to a stiff secondary matrix and (ii) a loss of rigidity sensing through YAP, as compared to stiff-primed cells. The mechanical adaptation resulted in a differential expression of miR-21, inversely proportional to the priming rigidity. The long-term mechanical memory retained by miR-21 unveiled a previously unidentified mechanical modulation of drug resistance by past matrix stiffness. The higher expression of miR-21 in soft-primed cells correlated with the increased resistance to gemcitabine, as compared to stiff-primed and non-primed pancreatic cancer cells.

scholarly journals Slug-Dependent Upregulation of L1CAM Is Responsible for the Increased Invasion Potential of Pancreatic Cancer Cells following Long-Term 5-FU Treatment

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0123684 ◽  
Author(s):  
Kaja Lund ◽  
Jennifer L. Dembinski ◽  
Nina Solberg ◽  
Alfonso Urbanucci ◽  
Ian G. Mills ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Invasion Potential ◽  
Pancreatic Cancer Cells

scholarly journals Investigation of long-term effect of Black Sea bee’s venom on the cytotoxicity of pancreatic cancer cells

2019 ◽  
pp. 1-6
Author(s):  
Selcen Çelik Uzuner ◽  
Sinan Tetikoğlu ◽  
Esra Birinci ◽  
Aytan Adilova ◽  
Sevgi Kolaylı
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Black Sea ◽  
Term Effect ◽  
Pancreatic Cancer Cells ◽  
Long Term Effect

scholarly journals Carboxyl-terminal domain of MUC16 imparts tumorigenic and metastatic functions through nuclear translocation of JAK2 to pancreatic cancer cells

Oncotarget ◽  
2015 ◽  
Vol 6 (8) ◽  
pp. 5772-5787 ◽  
Author(s):  
Srustidhar Das ◽  
Satyanarayana Rachagani ◽  
Maria P. Torres-Gonzalez ◽  
Imayavaramban Lakshmanan ◽  
Prabin D. Majhi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Terminal Domain ◽  
Pancreatic Cancer Cells ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal

scholarly journals TGF-β downregulates PTEN via activation of NF-κB in pancreatic cancer cells

2010 ◽  
Vol 298 (2) ◽  
pp. G275-G282 ◽  
Author(s):  
Jimmy Y. C. Chow ◽  
Makiko Ban ◽  
Helen L. Wu ◽  
Flang Nguyen ◽  
Mei Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Dominant Negative ◽  
Boyden Chamber ◽  
Western Blots ◽  
Smad Signaling ◽  
Pancreatic Cancers ◽  
Pancreatic Cancer Cells

TGF-β utilizes receptor-activated SMAD signaling to mediate growth suppression; however, non-SMAD signaling that modulates the TGF-β response in epithelial cells become apparent when the SMAD signaling is abrogated, a common occurrence in pancreatic cancers. Here, we examined whether TGF-β utilized NF-κB to downregulate PTEN, a gene that is rarely mutated in pancreatic cancers. SMAD4-null BxPc3 and CAPAN-1 pancreatic cancer cells were treated with TGF-β (10 ng/ml) and lysed, and cellular proteins were analyzed by Western blots using p-IκB, p65, and PTEN antibodies. PTEN promoter and NF-κB activities were assessed by PTEN-luc and p-NF-luc constructs, respectively. Dominant negative p-IκB-α-M (NF-κB superrepressor) was used to block activation of NF-κB. Cell motility was assessed by Boyden chamber migration assay. TGF-β induced IκB-α phosphorylation followed by NF-κB p65 subunit nuclear translocation and increased NF-κB activity. IκB-α-M blocked TGF-β-induced NF-κB activity, reversed downregulated PTEN promoter activity and PTEN expression, and prevented augmentation of cell motility induced by TGF-β. SMAD4 restoration, but not knockdown of SMAD2 and/or 3, reversed TGF-β-induced NF-κB activity. Thus TGF-β suppresses PTEN in pancreatic cancer cells through NF-κB activation and enhances cell motility and invasiveness in a SMAD4-independent manner that can be counteracted when TGF-β-SMAD signaling is restored. The TGF-β/NF-κB/PTEN cascade may be a critical pathway for pancreatic cancer cells to proliferate and metastasize.

scholarly journals Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 614
Author(s):  
Juan Du ◽  
Rory S. Carroll ◽  
Garett J. Steers ◽  
Brett A. Wagner ◽  
Brianne R. O’Leary ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Standard Of Care ◽  
Related Factor ◽  
Dual Roles ◽  
Normal Cells ◽  
Pancreatic Cancer Cells ◽  
Radiation Induced ◽  
Long Term Survivors

Pancreatic cancer cells (PDACs) are more susceptible to an oxidative insult than normal cells, resulting in greater cytotoxicity upon exposure to agents that increase pro-oxidant levels. Pharmacological ascorbate (P-AscH−), i.e., large amounts given intravenously (IV), generates significant fluxes of hydrogen peroxide (H2O2), resulting in the killing of PDACs but not normal cells. Recent studies have demonstrated that P-AscH− radio-sensitizes PDAC but is a radioprotector to normal cells and tissues. Several mechanisms have been hypothesized to explain the dual roles of P-AscH− in radiation-induced toxicity including the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2), RelB, as well as changes in bioenergetic profiles. We have found that P-AscH− in conjunction with radiation increases Nrf2 in both cancer cells and normal cells. Although P-AscH− with radiation decreases RelB in cancer cells vs. normal cells, the knockout of RelB does not radio-sensitize PDACs. Cellular bioenergetic profiles demonstrate that P-AscH− with radiation increases the ATP demand/production rate (glycolytic and oxidative phosphorylation) in both PDACs and normal cells. Knocking out catalase results in P-AscH− radio-sensitization in PDACs. In a phase I trial where P-AscH− was included as an adjuvant to the standard of care, short-term survivors had higher catalase levels in tumor tissue, compared to long-term survivors. These data suggest that P-AscH− radio-sensitizes PDACs through increased peroxide flux. Catalase levels could be a possible indicator for how tumors will respond to P-AscH−.

scholarly journals Restore of miR-541 resensitizes pancreatic cancer cells to gemcitabine-induced apoptosis through suppression of HAX-1

2020 ◽  
Author(s):  
Hong Liu ◽  
Xuemei Gan ◽  
Jun Zhang ◽  
Xingdiao Zhang ◽  
Jie Xiong ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Luciferase Reporter ◽  
Pancreatic Cancer Cells ◽  
Reporter Assays ◽  
Potential Strategy ◽  
Induced Apoptosis ◽  
Mtt Assays

Abstract Background: MiR-541 acts as a tumor suppressor in some cancers. However, the role of miR-541 in regulating the chemosensitivity to cancer cells is still unclear. The aim of this study is to explore the effect of miR-541 on chemoresistance of pancreatic cancer (PCa) cells to gemcitabine-induced apoptosis.Methods: Gemcitabine-resistant Panc-1 and Capan-2 PCa cell lines (Panc-1/R and Capan-2/R) were established through long term exposure to gemcitabine. Effect of miR-541 on changing the sensitivity of Panc-1/R and Capan-2/R to gemcitabine-induced cytotoxicity was evaluated by MTT assays. Regulation of miR-541 on HAX-1 was confirmed by bioinformatics, western blot analysis and luciferase reporter assays. Cell apoptosis and mitochondrial membrane potential (MMP) was measured by flow cytometry analysis.Results: Comparison with Panc-1 and Capan-2, downregulation of miR-541 was observed in Panc-1/R and Capan-2/R cells. Overexpression of miR-541 was found to increase the cytotoxicity of gemcitabine to Panc-1/R and Capan-2/R cells. However, transfection with HAX-1 plasmid can abolish the effect of miR-541 on gemcitabine-induced cytotoxicity against Panc-1/R and Capan-2/R.Conclusion: Downregulation of miR-541 is responsible for development of gemcitabine resistance in PCa. Overexpression of miR-541 may represent a potential strategy to reverse the chemoresistance of PCa.

The Long-Term Fate of the Sonoporated Pancreatic Cancer Cells is Uncorrelated With the Degree of Model Molecular Loading

2020 ◽  
Vol 46 (4) ◽  
pp. 1015-1025
Author(s):  
Lizhou Lin ◽  
Mouwen Cheng ◽  
Rong Wu ◽  
Qiusheng Shi ◽  
Lianfang Du ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cells

scholarly journals miR-33a suppresses the nuclear translocation of β-catenin to enhance gemcitabine sensitivity in human pancreatic cancer cells

Tumor Biology ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 9395-9403 ◽  
Author(s):  
Chen Liang ◽  
Zhen Wang ◽  
Ying-Yi Li ◽  
Bao-Hua Yu ◽  
Fei Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6080
Author(s):  
Gabrielle Wishart ◽  
Priyanka Gupta ◽  
Andrew Nisbet ◽  
Giuseppe Schettino ◽  
Eirini Velliou
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Collagen I ◽  
Cancer Tissue ◽  
Pancreatic Cancer Cells ◽  
Post Radiation ◽  
The Impact ◽  
Radiotherapy Treatment

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.

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