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Distant metastasis is a primary cause of mortality and contributes to poor surgical outcomes in cancer patients. Before the development of organ-specific metastasis, the formation of a pre-metastatic niche is pivotal in promoting the spread of cancer cells. This review delves into the intricate landscape of the pre-metastatic niche, focusing on the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The discussion encompasses cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells, in addition to molecular factors like secreted substances from tumors and extracellular vesicles, within the framework of pre-metastatic niche formation. Insights into the temporal mechanisms of pre-metastatic niche formation such as epithelial-mesenchymal transition, immunosuppression, extracellular matrix remodeling, metabolic reprogramming, vascular permeability and angiogenesis are provided. Furthermore, the landscape of pre-metastatic niche in different metastatic organs like lymph nodes, lungs, liver, brain, and bones is elucidated. Therapeutic approaches targeting the cellular and molecular components of pre-metastatic niche, as well as interventions targeting signaling pathways such as the TGF-β, VEGF, and MET pathways, are highlighted. This review aims to enhance our understanding of pre-metastatic niche dynamics and provide insights for developing effective therapeutic strategies to combat tumor metastasis.
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http://dx.doi.org/10.1038/s41392-024-01937-7 | DOI Listing |
Nan Fang Yi Ke Da Xue Xue Bao
August 2025
School of Mathematics and Statistics, Guangdong University of Technology, Guangzhou 510520, China.
Objectives: To explore the key role of myeloid-derived suppressive cells (MDSCs) in pre-metastatic niche (PMN) and analyze their interrelationships with the main components in the microenvironment using a mathematical model.
Methods: Mathematical descriptions were used to systematically analyze the functions of MDSCs in tumor metastasis and elucidate their association with the major components (vascular endothelial cells, mesenchymal stromal cells, and cancer-associated macrophages) contributing to the formation of the pre-metastatic microenvironment. Based on the formation principle of the pre-metastatic microenvironment of tumors, the key biological processes were assumed to construct a coupled partial differential diffusion equation model.
Trends Cancer
September 2025
Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China; Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, 310058, China. Electronic address:
Glucose restriction generally limits tumor growth. Recently, Wu et al. reported that glucose restriction inhibits primary tumors but promotes lung metastasis by forming a macrophage-dominated, natural killer (NK) cell-deficient pre-metastatic niche (PMN).
View Article and Find Full Text PDFFront Oncol
August 2025
Stroke Unit, Emergency Department, Umberto I Hospital, Sapienza University of Rome, Rome, Italy.
The association between ischemic stroke (IS) and malignancy is well established. Cancer-related strokes are predominantly embolic and classified as embolic strokes of undetermined source (ESUS). While malignancy-associated coagulopathy represents the primary pathogenic mechanism, neoplastic embolization of circulating tumor cells is another potential etiology, particularly in cases of cardiac and pulmonary malignancies.
View Article and Find Full Text PDFPharmaceuticals (Basel)
July 2025
Department of Anatomy and Genetics, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as and , alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT).
View Article and Find Full Text PDFFront Immunol
August 2025
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, whose progression is intimately linked to the complex dynamics of the tumor microenvironment (TME). Exosomes, once considered mere cellular waste, have emerged as pivotal mediators of intercellular communication within the TME, actively participating in the multistep development of HCC. These nanoscale vesicles play crucial roles in the initiation of precancerous lesions and, by transporting drug resistance-related molecules such as proteins and non-coding RNAs, facilitate the acquisition of resistance to chemotherapy and targeted therapies by tumor cells.
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