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 CD10GPR77 HFF subpopulation, but also the percentage of ALDH1 C91/PL cells. A non-cytotoxic acetylsalicylic acid treatment decreased HFF-induced ALDH1 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.
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http://dx.doi.org/10.3390/ijms221910562 | DOI Listing |
Pathogens
November 2024
Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Human T-cell leukemia virus type 1 (HTLV-1) infects CD4 T-cells through close cell-cell contacts. The viral Tax-1 (Tax) protein regulates transcription by transactivating the HTLV-1 promoter in the 5' long terminal repeat of the integrated provirus. Here, we generated a clonal Tax-responsive T-cell line to track HTLV-1 infection at the single-cell level using flow cytometry, bypassing intracellular viral protein staining.
View Article and Find Full Text PDFInt J Oncol
January 2023
Molecular Tumor-genesis and Anticancer Pharmacology, EDST, Lebanese university, Hadath, Lebanon.
Subsequently to the publication of the above article, a concerned reader drew to the attention of the Editorial Office and the authors that certain pairings of the GAPDH western blotting control bands in Fig. 4 appeared to be strikingly similar to adjacent pairings of bands within the same gel slices; moreover, data bands featured in the HuT‑2, C91‑PL and Jurkat zymography blots in Fig. 5 also appeared to be remarkably similar, both comparing the bands within a given gel slice (as in the case of the Jurkat cell experiment in Fig.
View Article and Find Full Text PDFInt J Mol Sci
September 2021
Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
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.
View Article and Find Full Text PDFFront Microbiol
October 2019
Institute of Clinical and Molecular Virology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for Adult T-Cell Leukemia/Lymphoma (ATLL) and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HTLV-1 infects CD4 T-cells via cell-to-cell transmission requiring reorganization of the cytoskeleton and expression of the viral transactivator and oncoprotein Tax. Viruses spread at the virological synapse (VS), a virus-induced specialized cell-cell contact, by polarized budding into synaptic clefts, and by cell surface transfer of viral biofilms (VBs).
View Article and Find Full Text PDFFront Microbiol
June 2018
Immunology and Molecular Oncology, Veneto Institute of Oncology, IOV - IRCCS, Padua, Italy.
Adult T cell Leukemia/Lymphoma (ATLL) is a mature T cell malignancy associated with Human T cell Leukemia Virus type 1 (HTLV-1) infection. Among its four main clinical subtypes, the prognosis of acute and lymphoma variants remains poor. The long latency (3-6 decades) and low incidence (3-5%) of ATLL imply the involvement of viral and host factors in full-blown malignancy.
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