Visualizing cancer extravasation: from mechanistic studies to drug development
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NON-THEMATIC REVIEW
Visualizing cancer extravasation: from mechanistic studies to drug development Xiao Cheng 1,2 & Ke Cheng 1,2 Received: 2 June 2020 / Accepted: 27 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Metastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of both in vitro and in vivo cancer extravasation models, that shed light on the underlying mechanisms. Specifically, multiple cancer extravasation stages, such as the adhesion to the endothelium and transendothelial migration, are successfully probed using these technologies. Moreover, the roles of different cell adhesive molecules, chemokines, and growth factors, as well as the mechanical factors in these stages are well illustrated. Deeper understandings of cancer extravasation mechanisms offer us new opportunities to escalate the discovery of anti-extravasation drugs and therapies and improve the prognosis of cancer patients. Keywords Cancer metastasis . Cancer cell extravasation . Cancer models . Cancer therapies
1 Introduction Metastasis is the most life-threatening aspect of cancer that roughly accounts for 90% of cancer-related death [1]. During metastasize dissemination, metastatic cancer cells from primary sites need to complete multiple steps to form metastases, including to (1) go through the epithelial-tomesenchymal transition (EMT) to acquire enhanced motility and resistance to apoptosis; (2) intravasate tumor blood vessels and enter the circulation; (3) survive from attacks of the immune cells and mechanical stress in the bloodstream; (4) extravasate the endothelium as single cell or clusters; and (5) form new colonization [1–5].
* Ke Cheng [email protected] 1
Joint Department of Biomedical Engineering, North Carolina State University & University of North Carolina at Chapel Hill, Raleigh, NC, USA
2
Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA
Among these steps, most of them have been successfully targeted in the past decades. For example, EMT can be inhibited by several non-coding RNAs (miR200 and miR205). The inhibition is achieved by regulating the expression of EMT-related transcription factors ZEB1, ZEB2, and Twist1/2 [6]. The intravasation of metastatic cancer cells can be restricted by interfering with the transforming growth factor-beta (TGFβ) [7] or the epidermal growth factor receptor (EGRF) signaling pathways [8]. Despite all the progress made in regulating one or more essenti
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