Search results for "Cell Dedifferentiation"
showing 4 items of 4 documents
Conversion of Nonproliferating Astrocytes into Neurogenic Neural Stem Cells: Control by FGF2 and Interferon-gamma
2016
Abstract Conversion of astrocytes to neurons, via de-differentiation to neural stem cells (NSC), may be a new approach to treat neurodegenerative diseases and brain injuries. The signaling factors affecting such a cell conversion are poorly understood, and they are hard to identify in complex disease models or conventional cell cultures. To address this question, we developed a serum-free, strictly controlled culture system of pure and homogeneous “astrocytes generated from murine embryonic stem cells (ESC).” These stem cell derived astrocytes (mAGES), as well as standard primary astrocytes resumed proliferation upon addition of FGF. The signaling of FGF receptor tyrosine kinase converted G…
Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation.
2012
Adoptive cell transfer therapies (ACTs) with cytotoxic T cells that target melanocytic antigens can achieve remissions in patients with metastatic melanomas, but tumours frequently relapse. Hypotheses explaining the acquired resistance to ACTs include the selection of antigen-deficient tumour cell variants and the induction of T-cell tolerance. However, the lack of appropriate experimental melanoma models has so far impeded clear insights into the underlying mechanisms. Here we establish an effective ACT protocol in a genetically engineered mouse melanoma model that recapitulates tumour regression, remission and relapse as seen in patients. We report the unexpected observation that melanoma…
Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells
2014
Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involv…
Controversial issues in soft tissue solitary fibrous tumors: A pathological and molecular review
2019
The clinical evolution of solitary fibrous tumor (SFT) remains unclear. Although various clinical, morphological and molecular criteria may indicate increased risk of malignancy, some SFT can still progress despite having a clearly benign appearance. Various risk stratification systems have been proposed, but unfortunately they are not sufficient to precisely determine the malignant potential. In this review, we discuss current knowledge on SFT, focusing on the following controversial issues: (i) the diverse morphologic spectrum: 'the great simulator;' (ii) malignant transformation or dedifferentiation; (iii) current risk stratification systems; and (iv) molecular factors associated with cl…