Mechanisms Involved in the Promoting Activity of Fibroblasts in HTLV-1-Mediated Lymphomagenesis: Insights into the Plasticity of Lymphomatous Cells
| Autor: | Rigotto, G., Montini, B., Mattiolo, A., Lazzari, N., Piano, M. A., Remondini, D., Marmiroli, S., Bertacchini, J., Chieco-bianchi, L., Calabro, M. L. |
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| Přispěvatelé: | Rigotto G., Montini B., Mattiolo A., Lazzari N., Piano M.A., Remondini D., Marmiroli S., Bertacchini J., Chieco-bianchi L., Calabro M.L. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
cancer stem cells
ATLL Cancer stem cells HTLV-1 Lymphomagenesis Plasticity Stemness Lymphoma QH301-705.5 Jurkat Cell Mice SCID Article Cell Line Jurkat Cells stemness lymphomagenesis Mice Inbred NOD Animals Humans Biology (General) Coculture Technique QD1-999 Cells Cultured Mice Knockout Human T-lymphotropic virus 1 Stemne Aspirin Animal Cancer stem cell Gene Expression Profiling Anti-Inflammatory Agents Non-Steroidal Fibroblasts Xenograft Model Antitumor Assays Coculture Techniques Gene Expression Regulation Neoplastic Lymphomagenesi Chemistry plasticity Neoplastic Stem Cells Fibroblast Neoplastic Stem Cell Human Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10562, p 10562 (2021) International Journal of Molecular Sciences Volume 22 Issue 19 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Among the mechanisms leading to progression to Adult T-cell Leukaemia/Lymphoma in Human T-cell Leukaemia Virus type 1 (HTLV-1)-infected subjects, the contribution of stromal components remains poorly understood. To dissect the role of fibroblasts in HTLV-1-mediated lymphomagenesis, transcriptome studies, cytofluorimetric and qRT-PCR analyses of surface and intracellular markers linked to plasticity and stemness in coculture, and in vivo experiments were performed. A transcriptomic comparison between a more lymphomagenic (C91/III) and the parental (C91/PL) cell line evidenced hyperactivation of the PI3K/Akt pathway, confirmed by phospho-ELISA and 2-DE and WB analyses. C91/III cells also showed higher expression of mesenchymal and stemness genes. Short-term coculture with human foreskin fibroblasts (HFF) induced these features in C91/PL cells, and significantly increased not only the cancer stem cells (CSCs)-supporting CD10+GPR77+ HFF subpopulation, but also the percentage of ALDH1bright C91/PL cells. A non-cytotoxic acetylsalicylic acid treatment decreased HFF-induced ALDH1bright C91/PL cells, downregulated mesenchymal and stemness genes in cocultured cells, and delayed lymphoma growth in immunosuppressed mice, thus hindering the supportive activity of HFF on CSCs. These data suggest that crosstalk with HFF significantly intensifies the aggressiveness and plasticity of C91/PL cells, leading to the enrichment in lymphoma-initiating cells. Additional research is needed to better characterize these preliminary findings. |
| Databáze: | OpenAIRE |
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