Epitelial-to-mesenchimal transition and invasion are upmodulated by tumor-expressed granzyme B and inhibited by docosahexaenoic acid in human colorectal cancer cells

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• 作者：Donatella D’Eliseo ; Giuliana Di Rocco…
• 关键词：Granzyme B ; Epithelial ; to ; mesenchymal transition ; Invasion ; Colorectal cancer ; Cancer stem cells ; Transforming growth factor ; β ; Docosahexaenoic acid ; ω ; 3 Polyunsaturated fatty acid ; Adjuvant cancer therapy
• 刊名：Journal of Experimental & Clinical Cancer Research
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：35
• 期：1
• 全文大小：2,081 KB
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• 作者单位：Donatella D’Eliseo (1) (2)
  Giuliana Di Rocco (3)
  Rossella Loria (3)
  Silvia Soddu (3)
  Angela Santoni (1)
  Francesca Velotti (2)
  
  1. Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161, Rome, Italy
  2. Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell’Università, 01100, Viterbo, Italy
  3. Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, 00144, Rome, Italy
  
• 刊物主题：Oncology; Cancer Research;
• 出版者：BioMed Central
• ISSN：1756-9966

文摘

Background Granzyme B (GrB) is a serine protease, traditionally known as expressed by cytotoxic lymphocytes to induce target cell apoptosis. However, it is emerging that GrB, being also produced by a variety of normal and neoplastic cells and potentially acting on multiple targets, might represent a powerful regulator of a wide range of fundamental biological processes. We have previously shown that GrB is expressed in urothelial carcinoma tissues and its expression is associated to both pathological tumor spreading and EMT. We have also shown that docosahexaenoic acid (DHA), a dietary ω-3 polyunsaturated fatty acid with anti-tumor activity, while inhibiting urothelial and pancreatic carcinoma cell invasion also inhibited their GrB expression in vitro. In this study, we characterized a panel of colorectal carcinoma (CRC) cells, with different invasive capabilities, for GrB expression and for the contribution of GrB to their EMT and invasive phenotype. In addition, we investigated the effect of DHA on CRC cell-associated GrB expression, EMT and invasion.