Edited by:
Leszek Kotula, MD, PhD, Upstate Medical University, United States of America
Submission Status: Open | Submission Deadline: 30 April 2025
Cellular & Molecular Biology Letters is calling for submissions to our Collection on Tumor Plasticity and Microenvironmental Heterogeneity in Metastasis.
Tumor Plasticity: Tumor plasticity refers to the intrinsic ability of cancer cells to dynamically change their phenotypic and functional characteristics in response to internal genetic mutations and external environmental cues. This adaptability is crucial for cancer progression and metastasis. Plasticity allows cancer cells to undergo processes such as the epithelial-mesenchymal transition (EMT) and the reverse mesenchymal-epithelial transition (MET), enabling them to detach from the primary tumor, invade surrounding tissues, survive in circulation, and eventually colonize distant organs. Additionally, tumor plasticity involves the interconversion between cancer stem cell-like states and more differentiated states, enhancing the tumor's capacity to resist therapies and regenerate after apparent remission.
Microenvironmental Heterogeneity: The tumor microenvironment (TME) is a complex and dynamic milieu composed of various non-cancerous cells, including fibroblasts, immune cells, endothelial cells, and components of the extracellular matrix. Microenvironmental heterogeneity refers to the variability in these cellular and acellular components not only within different regions of the same tumor but also between the primary and metastatic sites. This heterogeneity influences the behavior of cancer cells through mechanisms such as differential secretion of growth factors, cytokines, and chemokines, variations in mechanical pressure, hypoxia, and nutrient availability. These factors can either suppress or promote tumor growth and metastasis depending on their nature and the context.
Interaction and Impact on Metastasis: The interplay between tumor plasticity and microenvironmental heterogeneity is a key driver of metastatic spread. Plasticity enables cancer cells to respond and adapt to the heterogeneity of the microenvironment. For example, cancer cells can modify their metabolic pathways to survive in low-nutrient or hypoxic conditions commonly found within different tumor regions. Conversely, the microenvironment can induce plasticity in cancer cells, promoting EMT and other phenotypic changes necessary for metastasis. As cancer cells disseminate and establish at distant sites, they encounter and must adapt to new microenvironments, which may differ substantially from the primary site. The ability of metastatic cells to modulate or be modulated by these new microenvironments determines their success in forming secondary tumors. Therapeutic strategies targeting these interactions aim to disrupt the adaptive capabilities of cancer cells, thereby limiting their potential to metastasize and colonize distant organs. Understanding and targeting the dynamic interactions between tumor plasticity and microenvironmental heterogeneity hold promise for developing more effective interventions against cancer metastasis.
Here are essential topics that would enrich the review on the subject:
1. Mechanisms of Tumor Plasticity: Epithelial-Mesenchymal Transition (EMT) and Mesenchymal-Epithelial Transition (MET) processes and their implications in metastasis. The role of Cancer Stem Cells (CSCs) in tumor regeneration, resistance, and metastasis. How cancer cells adapt to therapeutic pressures and evade treatment?
2. Components of the Tumor Microenvironment (TME): Cellular Components: fibroblasts, immune cells, endothelial cells, and other stromal cells; The Extracellular Matrix (ECM) ECM's role in providing structural and biochemical support to tumors. The role of biochemical factors: growth factors, cytokines, and chemokines that influence tumor behavior.
3. Interactions Between Tumor Cells and the Microenvironment: How TME influences tumor growth, invasion, and metastasis? How tumor cells remodel the TME to facilitate their own survival and expansion?
4. Microenvironmental Heterogeneity Across Primary and Metastatic Sites: How cancer cells adapt to different organ-specific microenvironments during metastasis i.e. site-specific adaptations. How variations in the TME can lead to differential responses to treatment between the primary tumor and metastatic sites.
5. Targeting Tumor Plasticity and manipulating TME: Explore potential therapies that inhibit or reverse EMT, target CSCs, or exploit phenotypic vulnerabilities. What are the advantages of combining traditional therapies with treatments targeting tumor plasticity and the TME. What are the strategies to modify the TME to make it less conducive to tumor growth and metastasis.
A review encompassing these subjects would not only offer a thorough exploration of tumor plasticity and microenvironmental heterogeneity but also provide insights into potential therapeutic avenues and future research directions in combating metastatic cancer.
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This Collection supports and amplifies research related to SDG 3: Good health and well-being.