Navegando por Palavras-chave "Células-tronco neuplásicas"
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- ItemEmbargoIsolamento de uma subpopulação de células de melanoma murino com características de progenitoras tumorais e análises de suas propriedades “tronculares” e tumorigênicas(Universidade Federal de São Paulo (UNIFESP), 2011-01-26) Nascimento, Telma Lisboa do [UNIFESP]; Ferreira, Alice Teixeira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Melanoma is one of the most aggressive tumors and its resistance to many current therapeutic modalities is a well known fact. It is plausible to conjecture that this resistance is intimately related to the presence of a subpopulation of tumor stem cells. Following this idea we develop an experimental model with melanoma lineages whose cells present properties of stem cells, used: EGF (Epidermal Growth Factor), bFGF ("basic factor Growth Factor), LIF (Leukemia Inhibitory Factor") and retinoic acid. These cells were originated by long-term cultures (over 8 months) under special medium. A process of dedifferentiation forming adherents and non-adherents spheres has been clearly identified; cells from those spheres express stem cell markers and plasticity to transdifferentiation into other cellular types (neural-like, melanocytic-like and fibroblastic-like) have been observed. In vivo experiments with these cells reveal increased malignancy with significant growth of tumoral mass and larger ulceration when compared with control tumors. Oxidative stress played an important role in the survival of these cells during long-term cultures; protecting of apoptosis, and promoting the expression of anti-apoptotic protein Bcl-2. During in vivo experiments we also observed one case of spontaneous metastases to GI tract after 25 days of subcutaneous injection of melanoma tumor stem cells in mice. Based on these findings, we propose that melanoma lineages under special medium and after long-term cultures develop a subpopulation with more stable properties and characteristics of stem cells with direct consequences to malignancy.