FAT1: a potential target for monoclonal antibody therapy in colon cancer
| Autor: | Luigi Terracciano, Alberto Grandi, Matteo Parri, Ilaria Naldi, Guido Grandi, Chaojun Song, Elisa De Camilli, Susanna Campagnoli, Boquan Jin, Renata Grifantini, Caterina Cinti, Luisa Ganfini, Giuseppe Viale, Piero Pileri, Aurelien Lacombe, Paolo Sarmientos |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Proto-Oncogene Proteins B-raf
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Colorectal cancer colorectal cancer Antineoplastic Agents Apoptosis medicine.disease_cause BRAF 03 medical and health sciences Prostate cancer 0302 clinical medicine FAT1 Cell Line Tumor Internal medicine KRAS medicine Humans Monoclonal antibody therapy business.industry Antibodies Monoclonal Cancer immunohistochemistry monoclonal antibody Cadherins medicine.disease Cancer therapy FAT1 CRC-associated protein digestive system diseases ErbB Receptors 030104 developmental biology 030220 oncology & carcinogenesis Colonic Neoplasms Mutation Cancer cell ras Proteins Skin cancer Translational Therapeutics business Liver cancer HT29 Cells |
| Zdroj: | British Journal of Cancer 114 (2016): 40–51. doi:10.1038/bjc.2016.145 info:cnr-pdr/source/autori:Piero Pileri, Susanna Campagnoli, Alberto Grandi, Matteo Parri, Elisa De Camilli, Chaojun Song, Luisa Ganfini, Aurelien Lacombe, Ilaria Naldi, Paolo Sarmientos, Caterina Cinti, Boquan Jin, Guido Grandi, Giuseppe Viale, Luigi Terracciano and Renata Grifantini/titolo:FAT1: a potential target for monoclonal antibody therapy in colon cancer/doi:10.1038%2Fbjc.2016.145/rivista:British Journal of Cancer/anno:2016/pagina_da:40/pagina_a:51/intervallo_pagine:40–51/volume:114 British Journal of Cancer |
| DOI: | 10.1038/bjc.2016.145 |
| Popis: | Background: Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents have limited efficacy. Methods: The atypical cadherin FAT1 was discovered as a novel CRC-associated protein by using a monoclonal antibody (mAb198.3). FAT1 expression was assessed in CRC cells by immunohistochemistry (IHC), immunoblots, flow cytometry and confocal microscopy. In addition, in vitro and in vivo tumour models were done to assess FAT1 potential value for therapeutic applications. Results: The study shows that FAT1 is broadly expressed in primary and metastatic CRC stages and detected by mAb198.3, regardless of KRAS and BRAF mutations. FAT1 mainly accumulates at the plasma membrane of cancer cells, whereas it is only marginally detected in normal human samples. Moreover, the study shows that FAT1 has an important role in cell invasiveness while it does not significantly influence apoptosis. mAb198.3 specifically recognises FAT1 on the surface of colon cancer cells and is efficiently internalised. Furthermore, it reduces cancer growth in a colon cancer xenograft model. Conclusions: This study provides evidence that FAT1 and mAb198.3 may offer new therapeutic opportunities for CRC including the tumours resistant to current EGFR-targeted therapies. |
| Databáze: | OpenAIRE |
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