Background: When do metastasis-related traits emerge?

Cell states associated with invasion and metastasis were widely observed even in early colorectal tumors, and surrounding fibroblasts were found to induce tumor-cell plasticity. The findings suggest that some traits needed for metastasis may arise early in tumor evolution. They do not mean that cancer cells had actually reached other organs at an early stage.

A research highlight by Safia Danovi published in Nature Genetics on May 14, 2026, covered a study by Buissant des Amorie and colleagues. The researchers combined organoid studies with multi-omics analysis of primary tumors to examine cell states and the microenvironment in early tumors. When and how cancer acquires the ability to metastasize remains unclear; this study focused on relationships between tumor cells and surrounding cells.

Key findings: Plasticity in early tumors and fibroblasts

The researchers observed that a highly plastic oncofetal state was widespread in early tumors. “Oncofetal” describes a state in which cancer cells display traits associated with fetal development; plasticity refers to a cell’s capacity to change state. The observation in early tumors drew attention because this state is linked to invasion- and metastasis-related traits mainly discussed in later-stage disease.

At the boundary where tumors invaded surrounding tissue, oncofetal cells interacted with trophocyte-like cancer-associated fibroblasts. The two cell populations shared a local microenvironment resembling one found in normal mucosa. According to the highlight, co-culture experiments showed that these fibroblasts strongly induced tumor-cell plasticity. State changes observed in culture, alongside the relationships between cells identified in tissue, support the possibility that interactions between the two cell types contribute to the formation of the oncofetal state.

However, not all early tumors lead to metastasis. This means the oncofetal state alone is not sufficient to cause metastasis. The highlight says the researchers ruled out additional genomic events, but the public text does not describe the scope or methods of that analysis. It also raises the possibility that immune evasion plays an important role, although the evidence is insufficient to interpret this as an established mechanism.

Implications and outlook: Unanswered questions between cell states and actual metastasis

The findings point to a research direction that examines changes in cancer cells alongside the effects of surrounding fibroblasts to understand traits needed for metastasis. The central interpretation is that metastasis-related traits may emerge in the early microenvironment. The results cannot be taken as proof of actual movement through the bloodstream, dormancy in the liver, or the timing of metastasis in individual patients.

Follow-up studies will need to determine which early tumors with an oncofetal state progress to metastasis and how immune evasion contributes to that difference. The supplied highlight alone does not allow verification of the sample size, detailed experimental conditions, or quantitative effects. This material also does not report clinical outcomes for tests to predict patients’ metastatic risk or for preventive treatments.

This article is based on the public text of the Nature Genetics research highlight. The original Nature paper cited by the highlight has DOI 10.1038/s41586-026-10344-7; the full paper and supplementary materials were not included in this review.