RESUMO
Cell-free DNA is present in different biological fluids and when released by tumor cells may contribute to pro-tumor events such as malignant transformation of cells adjacent to the tumor and metastasis. Thus, this study analyzed the effect of tumor cell-free DNA, isolated from the blood of prostate cancer patients, on non-tumor prostate cell lines (RWPE-1 and PNT-2). To achieve this, we performed cell-free DNA quantification and characterization assays, evaluation of gene and miRNA expression profiling focused on cancer progression and EMT, and metabolomics by mass spectrometry and cellular migration. The results showed that tumor-free cell DNA was able to alter the gene expression of MMP9 and CD44, alter the expression profile of nine miRNAs, and increased the tryptophan consumption and cell migration rates in non-tumor cells. Therefore, tumor cell-free DNA was capable of altering the receptor cell phenotype, triggering events related to malignant transformation in these cells, and can thus be considered a potential target for cancer diagnosis and therapy.
Assuntos
Transformação Celular Neoplásica/genética , DNA Tumoral Circulante/efeitos adversos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , DNA Tumoral Circulante/análise , DNA Tumoral Circulante/isolamento & purificação , Progressão da Doença , Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Triptofano/metabolismoRESUMO
Gene therapy emerged as a mighty alternative for conventional treatment of multiple diseases. It has been defined as a product "that mediate their effects by transcription and/or translation of transferred genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or genetically engineered microorganisms. The products may be used to modify cells in vivo or transferred to cells ex vivo prior to administration to the recipient". The first therapeutic gene therapy human trial was conducted in 1990 by Michael R. Blaese, and besides its potential, the technique suffered a major drawback after the tragical death of Jesse Gelsinger, caused by his immune response against the viral vector used in his treatment. To date, gene therapy has regained some popularity and more than 2000 clinical trials are ongoing, most of them related to the treatment or prevention of various types of cancer. Nevertheless, some types of cancer contain a rare population of stem-like cells, capable of differentiation into tumor cells, promoting the re-incidence of tumors. Those cells are generally more resilient to chemotherapy and radiotherapy and are related to tumor initiation, progression, recurrence and metastasis. The human prostate cancer (PCa) is highly heterogeneous and multifactorial, and even the markers are not precise enough to predict the clinical outcome. Furthermore, even though currently therapies can efficiently remove the tumors, the re-incidence rates are high. Gene therapy offers a handful of treatments that can halt oncogenes activation, promote the expression of suppressor genes or target cancer cells directly and induce apoptosis. Besides the risks involved, gene therapy can be of great help in the treatment of cancers and other diseases. This review aims to address the safety and potential of different gene therapy strategies used in the treatment of cancers.
