Some days ago I found a very interesting news that said: “Liver stem cells are involved in the development of tumors”.
Malignant transformation of hepatocytes is the origin of most hepatocarcinomas, an aggressive liver tumor with high mortality rates. But these cells do not act alone. A study by scientists, at the National Cancer Research Center (CNIO), shows how hepatocytes "recruit" and "instruct" stem cells or liver progenitors, that contribute to the progression of lesions.
Hepatocytes
Liver with stem cells
"Cells, that cause liver cancer, as well as the beginning of their heterogeneity, are not yet clear and may depend on context", the authors write in the “Cell Reports” pages. Until now, hepatocytes --majority liver cells-- have been considered the main beginning of hepatocarcinomas, but the results of this research provide several nuances.
"What we show here is that the progenitor cells expand themselves, during the development of the tumors and, at a given moment, they are transformed due to the interaction with the oncogenic hepatocytes, which recruit them to participate in this process", explains Nabil Djouder, head of the Group of Growth Factors, Nutrients and Cancer of the CNIO and main author of the research.
Nabil Djouder at the CNIO
Thanks to an animal model --created by Djouder and his team--, which too accurately reproduces the process of tumor formation, in the human liver, and to various genetic experiments, the authors have tried to define the histopathology of the different tumors, that are developed in this organ, both benign (regenerative nodules, adenomas) and malignant (hepatocarcinoma or HCC).
"This is what we have observed: oncogenic hepatocytes give rise to hepatocellular carcinoma but, in this model that simulates human hepatocarcinogenesis, progenitor cells also participate. They do this mainly by causing benign tumors but, sometimes, aggressive carcinomas", says Djouder. That is, progenitor cells become oncogenic, even though in the early stages of tumor development they have not been transformed.
Malignant hepatocytes interact and instruct neighboring progenitor cells, to activate and maintain them, in an undifferentiated state, while they proliferate and expand themselves, which makes them oncogenic and contributes to the progression of lesions. This activation occurs, as this work shows, when hepatocytes secrete two molecules (alpha-ketoglutarate and galectin-3), that transform the progenitor cells.
"By blocking galectin-3, we were able to inhibit the interaction between these cells and we observed a reduction in tumor formation, a finding that could have therapeutic implications", says Djouder.
Well, this morning, I have listened on the radio to Mariano Barbacid (the Manager of the CNIO) and he complained talking about the lack of funding in Spanish scientific research. And I agree with him and hope that this lack changes as soon as possible.
Until my next post, kind regards, Luis.
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