Dataset Information

Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer.

ABSTRACT: Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood. Here, we tested the hypothesis that the site of tumor growth influences extra-hepatic metastasis formation. To this end, we implanted murine colon cancer organoids into the primary tumor site (i.e., the caecum) and into the primary metastasis site (i.e., the liver) in immunocompetent mice. The organoid-initiated liver tumors were significantly more efficient in seeding distant metastases compared to tumors of the same origin growing in the caecum (intra-hepatic: 51 vs. 40%, p = 0.001; peritoneal cavity: 51% vs. 33%, p = 0.001; lungs: 30% vs. 7%, p = 0.017). The enhanced metastatic capacity of the liver tumors was associated with the formation of 'hotspots' of vitronectin-positive blood vessels surrounded by macrophages. RNA sequencing analysis of clinical samples showed a high expression of vitronectin in liver metastases, along with signatures reflecting hypoxia, angiogenesis, coagulation, and macrophages. We conclude that 'onward spread' from liver metastases is facilitated by liver-specific microenvironmental signals that cause the formation of macrophage-associated vascular hotspots. The therapeutic targeting of these signals may help to contain the disease within the liver and prevent onward spread.

SUBMITTER: Wijler LA

PROVIDER: S-EPMC10930793 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer.

Wijler Liza A LA Viergever Bastiaan J BJ Strating Esther E van Schelven Susanne J SJ Poghosyan Susanna S Frenkel Nicola C NC Te Rietmole Hedy H Verheem Andre A Raats Danielle A E DAE Borel Rinkes Inne H M IHM Hagendoorn Jeroen J Kranenburg Onno O

Cancers 20240306 5

Colorectal cancer metastasizes predominantly to the liver but also to the lungs and the peritoneum. The presence of extra-hepatic metastases limits curative (surgical) treatment options and is associated with very poor survival. The mechanisms governing multi-organ metastasis formation are incompletely understood. Here, we tested the hypothesis that the site of tumor growth influences extra-hepatic metastasis formation. To this end, we implanted murine colon cancer organoids into the primary tum ...[more]

PMID: 38473429

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Project description:BackgroundThe emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 has caused widespread transmission around the world. As new epicentres in Europe and America have arisen, of particular concern is the increased number of imported coronavirus disease 2019 (COVID-19) cases in Africa, where the impact of the pandemic could be more severe. We aim to estimate the number of COVID-19 cases imported from 12 major epicentres in Europe and America to each African country, as well as the probability of reaching 10,000 cases in total by the end of March, April, May, and June following viral introduction.MethodsWe used the reported number of cases imported from the 12 major epicentres in Europe and America to Singapore, as well as flight data, to estimate the number of imported cases in each African country. Under the assumption that Singapore has detected all the imported cases, the estimates for Africa were thus conservative. We then propagated the uncertainty in the imported case count estimates to simulate the onward spread of the virus, until 10,000 cases are reached or the end of June, whichever is earlier. Specifically, 1,000 simulations were run separately under four different combinations of parameter values to test the sensitivity of our results.ResultsWe estimated Morocco, Algeria, South Africa, Egypt, Tunisia, and Nigeria as having the largest number of COVID-19 cases imported from the 12 major epicentres. Based on our 1,000 simulation runs, Morocco and Algeria's estimated probability of reaching 10,000 cases by end of March was close to 100% under all scenarios. In particular, we identified countries with less than 1,000 cases in total reported by end of June whilst the estimated probability of reaching 10,000 cases by then was higher than 50% even under the most optimistic scenario.ConclusionsOur study highlights particular countries that are likely to reach (or have reached) 10,000 cases far earlier than the reported data suggest, calling for the prioritization of resources to mitigate the further spread of the epidemic.

Dataset Information

Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer.

Publications

Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer.

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