In the realm of oncology, metastasis stands as the leading cause of mortality among cancer patients, often manifesting at diagnosis or surfacing years after initial treatment. This recurrence arises from disseminated tumor cells (DTCs) that had migrated early in the disease's lifespan, settling in secondary organs only to remain dormant before reactivation. This lurking threat underscores the urgency in understanding metastatic mechanisms and developing targeted interventions.

This Research Topic aims to provide an update on how the primary tumor secretome, DTCs, stromal cells, extracellular matrix (ECM) proteins, immune cells and pro-inflammatory mediators interact to govern organotropism, the formation of the pre-metastatic niche, and the critical decision between dormancy and metastatic activation. Such insights are crucial for devising new diagnostic and therapeutic strategies that could intervene before metastasis occurs or to prevent its reactivation.

To further our comprehension of these complex processes, contributions are sought, focusing on the interaction of immune/inflammatory cells and mediators with the ECM in establishing metastatic niches. We invite reviews, commentaries, and original research submissions, exploring, but not limited to, the following themes:
- Organotropism
- Novel mediators of the pre-metastatic and metastatic niches
- Roles of resident and infiltrating stromal cells, lymphoid and myeloid cells in niche formation
- Impact of immune/inflammatory cells and mediators, and of ECM proteins on metastatic activation
- Influence of immune/inflammatory cells and mediators on ECM composition within niches
- Advanced methodologies for analyzing pre-metastatic and metastatic niches

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic

Topic Editor Michal A. Rahat is the co-inventor of the following patents:
• Extracellular matrix metalloproteinase inducer (EMMPRIN) peptides and binding antibodies; WO/2013/150518
• Monoclonal antibodies targeting the human CD147/EMMPRIN protein; WO/2024/110956 A1.

Topic Editor Dalit Barkan is employed by VuJaDe Sciences. They are also the co-inventor of the following Patent Applications:
• CD11blow macrophages and conditioned media thereof for treating cancer and /or fibrosis; WO2014102799A1
• Apoptosis related protein in the TGF1-signaling pathway (ARTS) mimetic compounds, composition, methods and uses thereof in induction of differentiation of premalignant and malignant cells, thereby restoring their normal-like phenotype; WO2017077535A1
• The use of leptin in fertility; WO2003043652A2.
• Use of leptin in inhibition of endothelial cell proliferation; WO2001018040
• M. Leptin as an inhibitor of tumor cell proliferation; WO9848831.

All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Are you interested in contributing a manuscript to this Research Topic?

The Role of Immune and Stromal Mediators in the Formation of Pre-Metastatic and Metastatic Niches: The Gateway to Metastasis