A Bifunctional Molecule with Lectin and Protease Inhibitor Activities Isolated from Crataeva tapia Bark Significantly Affects Cocultures of Mesenchymal Stem Cells and Glioblastoma Cells
| Autor: | Fabricio Pereira Batista, Mariana Cristina Cabral Silva, Rodrigo da Silva Ferreira, Patrícia Maria Guedes Paiva, Tamara Lah Turnšek, Bruno Ramos Salu, Maria Tereza dos Santos Correia, Helena Motaln, Maria Luiza Vilela Oliva, Camila Ramalho Bonturi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cell cycle checkpoint
Cell Pharmaceutical Science Analytical Chemistry 0302 clinical medicine Cell Movement Drug Discovery U87 0303 health sciences Chemistry Cell Cycle medicine.anatomical_structure Chemistry (miscellaneous) 030220 oncology & carcinogenesis plant lectin Plant Bark Molecular Medicine Cytokines Plant Lectins Stromal cell Cell Survival Capparaceae Nitric Oxide Article lcsh:QD241-441 protease inhibitor 03 medical and health sciences Paracrine signalling lcsh:Organic chemistry Cell Line Tumor medicine Cell Adhesion Humans Protease Inhibitors Physical and Theoretical Chemistry neoplasms 030304 developmental biology Cell Proliferation Tumor microenvironment mesenchymal stem cells Plant Extracts Organic Chemistry Mesenchymal stem cell glioblastoma CrataBL microenvironment Coculture Techniques nervous system diseases Cancer cell Cancer research Metalloproteases |
| Zdroj: | Molecules Volume 24 Issue 11 Molecules, Vol 24, Iss 11, p 2109 (2019) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules24112109 |
| Popis: | Currently available drugs for treatment of glioblastoma, the most aggressive brain tumor, remain inefficient, thus a plethora of natural compounds have already been shown to have antimalignant effects. However, these have not been tested for their impact on tumor cells in their microenvironment-simulated cell models, e.g., mesenchymal stem cells in coculture with glioblastoma cell U87 (GB). Mesenchymal stem cells (MSC) chemotactically infiltrate the glioblastoma microenvironment. Our previous studies have shown that bone-marrow derived MSCs impair U87 growth and invasion via paracrine and cell&ndash cell contact-mediated cross-talk. Here, we report on a plant-derived protein, obtained from Crataeva tapia tree Bark Lectin (CrataBL), having protease inhibitory/lectin activities, and demonstrate its effects on glioblastoma cells U87 alone and their cocultures with MSCs. CrataBL inhibited U87 cell invasion and adhesion. Using a simplified model of the stromal microenvironment, i.e., GB/MSC direct cocultures, we demonstrated that CrataBL, when added in increased concentrations, caused cell cycle arrest and decreased cocultured cells&rsquo viability and proliferation, but not invasion. The cocultured cells&rsquo phenotypes were affected by CrataBL via a variety of secreted immunomodulatory cytokines, i.e., G-CSF, GM-CSF, IL-6, IL-8, and VEGF. We hypothesize that CrataBL plays a role by boosting the modulatory effects of MSCs on these glioblastoma cell lines and thus the effects of this and other natural lectins and/or inhibitors would certainly be different in the tumor microenvironment compared to tumor cells alone. We have provided clear evidence that it makes much more sense testing these potential therapeutic adjuvants in cocultures, mimicking heterogeneous tumor&ndash stroma interactions with cancer cells in vivo. As such, CrataBL is suggested as a new candidate to approach adjuvant treatment of this deadly tumor. |
| Databáze: | OpenAIRE |
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