Early dissemination primes the pre metastatic niche in the liver via neutrophil recruitment during the intestinal adenoma stage.

These datasets correspond to a manuscript currently in revision. Summary: Early dissemination refers to the spread of tumor cells to distant organs before they acquire the full capacity to form overt metastases. The contribution of this process to metastatic progression, and its prevalence across different types of cancer including colorectal, remain poorly understood. In this study, we uncovered the occurrence and significance of early dissemination during intestinal tumorigenesis—a previously unexplored phenomenon. Remarkably, we detected and characterized circulating intestinal cells in the blood of patients with benign adenomas, revealing that dissemination can occur at a pre-malignant stage. To determine the functional impact of this process, we developed a genetic mouse model enabling the study of early dissemination during the initial phases of intestinal tumorigenesis. Using this model, we identified mutated intestinal cells in both the blood and the liver already at the early adenoma stage. This early dissemination, including intestinal cells and specific cytokines, induces the establishment of a pre-metastatic niche, characterized by neutrophil enrichment in the liver, which in turn facilitated later colonization by aggressive cancer cells. Collectively, our findings provide the first clinical evidence that early dissemination occurs in patients with intestinal adenomas and demonstrate its critical role in shaping the metastatic microenvironment in mice. Beyond advancing our understanding of metastatic biology, these results open translational perspectives for the early detection of high-risk patients and the development of preventive strategies targeting the pre-metastatic niche before malignant progression occurs. More specifically, they include: raw_counts_CTCs.tsv – Raw gene count matrix obtained from bulk 3′ mRNA sequencing of circulating tumor cells (CTCs) isolated from three patients with intestinal adenomas and one healthy donor. M-989_IGF_Pannequin/ – Folder containing the raw data generated using the NanoString GeoMx Digital Spatial Profiler (DSP) platform for spatial transcriptomics analysis.