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Review
. 2025 Mar 17;23(1):340.
doi: 10.1186/s12967-025-06328-2.

Understanding pre-metastatic niche formation: implications for colorectal cancer liver metastasis

Yaqin Li  1   2 , Hong Wang  1   2 , Dengxuan Mao  1   2 , Xiaoyu Che  1   2 , Yan Chen  3   4   5 , Yuping Liu  6   7   8
Affiliations
Review

Understanding pre-metastatic niche formation: implications for colorectal cancer liver metastasis

Yaqin Li et al. J Transl Med. .

Abstract

The liver is the most commonly metastasized organ in colorectal cancer (CRC), and distant metastasis is the primary cause of mortality from CRC. In recent years, researchers have discovered that tumor cells create a "pre-metastatic niche (PMN)" favorable to metastasis before reaching the metastatic location. This review discusses the many processes and mechanisms that lead to PMN formation in CRC, including gut microbiota, stem cell stimulation, immunocyte interactions, and the induction of extracellular vesicles that carry important information. It examines research methods and diagnostic and therapeutic approaches for treating metastatic CRC with PMN. The crucial significance of PMN formation in metastatic CRC is also highlighted.

Keywords: Colorectal cancer; Liver metastasis; Pre-metastatic niche.

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Conflict of interest statement

Declarations. Conflict of interest: No competing interest.

Figures

Fig. 1
Fig. 1
Effects of exosome on PMN of CRC formation. CRC exosomal ncRNAs and protein can regulate a variety of stromal cells such as CAFs, immune cells such as TAM, et. to promote angiogenesis, EMT and the formation of inflammatory PMNs via different signaling pathways
Fig. 2
Fig. 2
Effects of gut microecology on PMN of CRC formation. Intestinal bacteria release tumor-promoting inflammatory factors such as IL-8, regulate neutrophil extracellular traps, promote vascular damage, and accelerate immune suppression to create a pro-inflammatory microenvironment
Fig. 3
Fig. 3
Effects of immune cells and stem cells on PMN of CRC formation. Immune cells, such as MDSC, T lymphocytes and neutrophils, regulate angiogenesis through multiple signaling pathways and form an immunosuppressive PMN. In addition, other factors such as diet and obesity also promote the formation of PMN by regulating the crosstalk between liver and CRC
Fig. 4
Fig. 4
Prevention and treatment strategies against CRCLM based on PMN. A radiomic approach combined with clinical characteristics is intended to diagnosis metastatic niches early. Organoids derived from mice and patient samples provide improved models and evaluation systems for PMN mechanisms research and drug development in CRCs. Traditional Chinese medicine compound preparations and plant-derived natural ingredients show promise in regulating PMN and potentially preventing CRCLM
See this image and copyright information in PMC

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