image: Figure 8: Schematic of the Mary-X xenograft/spheroidgenesis model of tumor dormancy Schematic depicts the Mary-X xenograft/spheroidgenesis sequence (A–G) which initiates tumor dormancy in vivo within the lymphovascular tumor emboli (C) and in vitro during spontaneous spheroidgenesis (D–G). The latter stages of this sequence result in the release of dormancy when the dormant spheroids (G) are reinjected into mice (H) with the subsequent emergence of Mary-X (I).
Credit: 2024 Ye et al.
“Both our experimental as well as observational studies indicate that in vivo lymphovascular tumor emboli and their in vitro spheroid equivalent initiate dormancy through these pathways.”
BUFFALO, NY- October 30, 2024 – A new research paper was published in Oncotarget's Volume 15 on October 11, 2024, entitled “Initiation of tumor dormancy by the lymphovascular embolus.”
Researchers Yin Ye, Justin Wang, Michael G. Izban, Billy R. Ballard, and Sanford H. Barsky from Meharry Medical College in Nashville, TN, and Scripps Mercy Hospital in San Diego, CA, uncovered critical mechanisms that lead to tumor dormancy in breast cancer. This study sheds light on how certain cancer cells can remain dormant for years before potentially reawakening as metastatic tumors.
Using breast cancer patient-derived organoids and tumor samples, the research team discovered that tumor dormancy in breast cancer can be triggered by specific signaling changes within small cell clusters, called tumor emboli, which detach from the primary tumor and travel through the bloodstream. These emboli can remain inactive, sometimes for years, before reawakening in other parts of the body. Key changes include reduced activity of mTOR, a metabolic regulator, and structural shifts in E-cadherin, a molecule involved in cell adhesion. This study also suggests these changes are regulated by the PI3K pathway and occur within the unique three-dimensional structure of tumor spheroids, shedding light on the interactions within dormant cell clusters.
As a conclusion, this work not only identifies mTOR and E-cadherin as key components in maintaining dormancy but also offers a promising roadmap for future therapies. By targeting these pathways, there may be potential to keep cancer cells in a dormant state, reducing the risk of late-stage recurrence and improving patient outcomes.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28658
Correspondence to: Sanford H. Barsky - sbarsky@mmc.edu
Keywords: cancer, dormancy, lymphovascular embolus, mTOR, E-cadherin proteolysis
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Not applicable
Article Title
Initiation of tumor dormancy by the lymphovascular embolus
Article Publication Date
11-Oct-2024
COI Statement
The authors declare that they, at the present time, have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. None of the sources of support listed influenced the collection, analysis and interpretation of data, the generation of the hypothesis, the writing of the manuscript or the decision to submit the manuscript for publication.