Low-Intensity Sonoporation-Induced Intracellular Signalling of Pancreatic Cancer Cells, Fibroblasts and Endothelial Cells
| Autor: | Spiros Kotopoulis, Odd Helge Gilja, Elisa Thodesen Murvold, Anika Langer, Ragnhild Haugse, Daniela Elena Costea, Emmet McCormack, Bjørn Tore Gjertsen, Gorka Ruiz de Garibay |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell type
Stromal cell Cell pancreatic cancer lcsh:RS1-441 Pharmaceutical Science Cellular homeostasis Article microbubbles Flow cytometry lcsh:Pharmacy and materia medica 03 medical and health sciences 0302 clinical medicine cellular stress medicine sonoporation 030304 developmental biology 0303 health sciences medicine.diagnostic_test Chemistry ultrasound phosphorylation Electroporation intracellular signaling ultrasound contrast agents Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell drug delivery tumour microenvironment Sonoporation |
| Zdroj: | Pharmaceutics Pharmaceutics, Vol 12, Iss 1058, p 1058 (2020) Volume 12 Issue 11 |
| ISSN: | 1999-4923 |
| Popis: | The use of ultrasound (US) and microbubbles (MB), usually referred to as sonoporation, has great potential to increase the efficacy of chemotherapy. However, the molecular mechanisms that mediate sonoporation response are not well-known, and recent research suggests that cell stress induced by US + MBs may contribute to the treatment benefit. Furthermore, there is a growing understanding that the effects of US + MBs are beyond only the cancer cells and involves the tumour vasculature and microenvironment. We treated pancreatic cancer cells (MIA PaCa-2) and stromal cells, fibroblasts (BJ) and human umbilical vein endothelial cells (HUVECs), with US ± MB, and investigated the extent of uptake of cell impermeable dye (calcein, by flow cytometry), viability (cell count, Annexin/PI and WST-1 assays) and activation of a number of key proteins in important intracellular signalling pathways immediately and 2 h after sonoporation (phospho flow cytometry). Different cell types responded differently to US ± MBs in all these aspects. In general, sonoporation induces immediate, transient activation of MAP-kinases (p38, ERK1/2), and an increase in phosphorylation of ribosomal protein S6 together with dephosphorylation of 4E-BP1. The sonoporation stress-response resembles cellular responses to electroporation and pore-forming toxins in membrane repair and restoring cellular homeostasis, and may be exploited therapeutically. The stromal cells were more sensitive to sonoporation than tumoural cells, and further efforts in optimising sonoporation-enhanced therapy should be targeted at the microenvironment. |
| Databáze: | OpenAIRE |
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