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Discovery of why colon cancer metastasis always follows the same invasive pattern

By 2 de June de 2014November 18th, 2020No Comments
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In black, the lung; in green, tumour cells dividing in the lung (Microscope image: J Urosevic, IRB)
 02.06.2014

Discovery of why colon cancer metastasis always follows the same invasive pattern

A team of scientists led by Roger Gomis, ICREA researcher and head of the Growth Control and Cancer Metastasis Group at the Institute for Research in Biomedicine (IRB Barcelona), has identified the genes that favour staggered colon cancer metastasis. Published on Sunday in the journal Nature Cell Biology (doi:10.1038/ncb2977), in addition to Gomis, the authors include Angel R. Nebreda, ICREA and BBVA Cancer Research Professor, and Eduard Batlle, ICREA Professor and head of the Colorectal Cancer Lab, both at IRB Barcelona.


Of the colon cancer patients that develop metastases, 40% present metastasis first to the liver and later to the lung, always in this clinical order of appearance. Although this staggered behavioural pattern was known, it was not understood at the molecular level.

The study reveals that the metastatic lesion in the liver is necessary for later metastasis to lung to occur, the former thus becoming a platform from which the cells prepare the subsequent lung metastatic niche to be colonized. The first authors of the study Jelena Urosevic and Xabier Garcia-Albéniz are postdoctoral researchers with Gomis’ group and the latter is also affiliated to the Hospital Clínic de Barcelona-IDIBAPS.

The researchers observed that established metastatic cells in the liver release a molecule called PTHLH. This molecule affects the cells of pulmonary blood vessels, which respond to PTHLH by triggering remodelling processes. When a tumour cells escapes from the liver to travel towards the lung, it releases more PTHLH, thus further stimulating the process. This causes the previously impermeable blood vessel walls to form gaps, which the metastatic cell exploits to cross into and colonize the lung.

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