Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

Kariri, Yousif A; Aleskandarany, Mohammed A; Joseph, Chitra; Toss, Michael S; Kurozumi, Sasagu; Mohammed, Omar J; Green, Andrew R; Rakha, Emad A

Abstract

Lymphovascular invasion (LVI) is associated with poor outcome in breast cancer (BC); however, its underlying mechanisms remain ill-defined. LVI in BC develops through complex molecular pathways involving not only the interplay with the surrounding microenvironment along with endothelial cells lining the lymphovascular spaces but also changes in the malignant epithelial cells with the acquisition of more invasion and migration abilities. In this review, we focus on the key features that enable tumour cell detachment from the primary niche, their migration and interaction with the surrounding microenvironment as well as the crosstalk with the vascular endothelial cells, which eventually lead to intravasation of tumour cells and LVI. Intravascular tumour cells emboli survival and migration, their distant site extravasation, stromal invasion and growth are part of the metastatic cascade. Cancer cell migration commences with loss of tumour cells’ cohesion initiating the invasion and migration processes which are usually accompanied by the accumulation of specific cellular and molecular changes that enable tumour cells to overcome the blockades of the extracellular matrix, spread into surrounding tissues and interact with stromal cells and immune cells. Thereafter, tumour cells migrate further via interacting with lymphovascular endothelial cells to penetrate the vessel wall leading ultimately to intravasation of cancer cells. Exploring the potential factors influencing cell migration in LVI can help in understanding the underlying mechanisms of LVI to identify targeted therapy in BC.

Citation

Kariri, Y. A., Aleskandarany, M. A., Joseph, C., Toss, M. S., Kurozumi, S., Mohammed, O. J., …Rakha, E. A. (2020). Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype. Pathobiology, 87, 218–231. https://doi.org/10.1159/000508337

• Journal Article Type: Review
• Acceptance Date: Apr 30, 2020
• Online Publication Date: Jul 9, 2020
• Publication Date: Jul 9, 2020
• Deposit Date: Apr 29, 2020
• Publicly Available Date: Jul 10, 2021
• Journal: Pathobiology
• Print ISSN: 1015-2008
• Electronic ISSN: 1423-0291
• Publisher: Karger Publishers
• Peer Reviewed: Peer Reviewed
• Volume: 87
• Pages: 218–231
• DOI: https://doi.org/10.1159/000508337
• Keywords: vascular invasion; breast cancer; cell migration; molecular mechanisms; Cancer stem cells
• Public URL: https://nottingham-repository.worktribe.com/output/4359065
• Publisher URL: https://www.karger.com/Article/FullText/508337
• Additional Information: This is the peer-reviewed but unedited manuscript version of the following article: Kariri Y, A, Aleskandarany M, A, Joseph C, Kurozumi S, Mohammed O, J, Toss M, S, Green A, R, Rakha E, A: Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype. Pathobiology 2020. doi: 10.1159/000508337. The final, published version is available at https://www.karger.com/Article/FullText/508337.