Background: Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo.
Methods: Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated.
Results: The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs.
Conclusions: Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs.
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http://dx.doi.org/10.1186/s13046-021-02167-3 | DOI Listing |
Viruses
December 2024
Department of Applied Biochemistry, Institute of Biotechnology, Technische Universität Berlin, 13355 Berlin, Germany.
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December 2024
1st Internal Medicine Department, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 55436 Thessaloniki, Greece.
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December 2024
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Achieving the precise targeting of lentiviral vectors (LVs) to specific cell populations is crucial for effective gene therapy, particularly in cancer treatment where the modulation of the tumor microenvironment can enhance anti-tumor immunity. Programmed cell death protein 1 (PD-1) is overexpressed on activated tumor-infiltrating T lymphocytes, including regulatory T cells that suppress immune responses via FOXP3 expression. We developed PD1-targeted LVs by incorporating the anti-PD1 nanobody nb102c3 into receptor-blinded measles virus H and VSV-G glycoproteins.
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December 2024
Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Vesicular stomatitis virus (VSV) represents a significant advancement in therapeutic medicine, offering unique molecular and cellular characteristics that make it exceptionally suitable for medical applications. The bullet-shaped morphology, RNA genome organization, and cytoplasmic replication strategy provide fundamental advantages for both vaccine development and oncolytic applications. VSV's interaction with host cells through the low-density lipoprotein receptor (LDL-R) and its sophisticated transcriptional regulation mechanisms enables precise control over therapeutic applications.
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