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LGR5 marks targetable tumor-initiating cells in mouse liver cancer

Cao, Wanlu ; Li, Meng ; Liu, Jiaye ; Zhang, Shaoshi ; Noordam, Lisanne ; Verstegen, Monique M A ; Wang, Ling ; Ma, Buyun ; Li, Shan ; Wang, Wenshi ; Bolkestein, Michiel ; Doukas, Michael ; Chen, Kan ; Ma, Zhongren ; Bruno, Marco ; Sprengers, Dave ; Kwekkeboom, Jaap ; van der Laan, Luc J W ; Smits, Ron ; Peppelenbosch, Maikel P ; Pan, Qiuwei

Nature communications, 2020-04, Vol.11 (1), p.1961-16, Article 1961 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
LGR5 marks targetable tumor-initiating cells in mouse liver cancer
Autor: Cao, Wanlu ; Li, Meng ; Liu, Jiaye ; Zhang, Shaoshi ; Noordam, Lisanne ; Verstegen, Monique M A ; Wang, Ling ; Ma, Buyun ; Li, Shan ; Wang, Wenshi ; Bolkestein, Michiel ; Doukas, Michael ; Chen, Kan ; Ma, Zhongren ; Bruno, Marco ; Sprengers, Dave ; Kwekkeboom, Jaap ; van der Laan, Luc J W ; Smits, Ron ; Peppelenbosch, Maikel P ; Pan, Qiuwei
Assuntos: Ablation ; Ablation Techniques ; Animals ; Antineoplastic Agents - therapeutic use ; Biomarkers, Tumor - metabolism ; Cancer ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; Carcinoma, Hepatocellular - therapy ; Combined Modality Therapy ; Disease resistance ; Drug Resistance, Neoplasm ; Female ; Fluorouracil - therapeutic use ; Hepatocellular carcinoma ; Hepatocytes ; Humans ; Liver ; Liver cancer ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Liver Neoplasms - therapy ; Medical treatment ; Mice ; Neoplastic Stem Cells - metabolism ; Organoids ; Receptors, G-Protein-Coupled - metabolism ; Stem cell transplantation ; Stem cells ; Therapeutic applications ; Therapeutic targets ; Tumor Cells, Cultured ; Tumors ; Up-Regulation ; Xenograft Model Antitumor Assays
É parte de: Nature communications, 2020-04, Vol.11 (1), p.1961-16, Article 1961
Descrição: Cancer stem cells (CSCs) or tumor-initiating cells (TICs) are thought to be the main drivers for disease progression and treatment resistance across various cancer types. Identifying and targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the enrichment of LGR5 expressing cells, a well-recognized stem cell marker, in mouse liver tumors, and the upregulation of LGR5 expression in human hepatocellular carcinoma. Isolated LGR5 expressing cells from mouse liver tumors are superior in initiating organoids and forming tumors upon engraftment, featuring candidate TICs. These cells are resistant to conventional treatment including sorafenib and 5-FU. Importantly, LGR5 lineage ablation significantly inhibits organoid initiation and tumor growth. The combination of LGR5 ablation with 5-FU, but not sorafenib, further augments the therapeutic efficacy in vivo. Thus, we have identified the LGR5 compartment as an important TIC population, representing a viable therapeutic target for combating liver cancer.
Editor: England: Nature Publishing Group
Idioma: Inglês

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LGR5 marks targetable tumor-initiating cells in mouse liver cancer

England: Nature Publishing Group

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