Storify Biology Showcases are deeper literature reviews that cover the history of a biomedical topic framed in an immersive viewer experience.
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Cancer Metastasis ~ Faster isn’t Better
Cancer kills by metastasizing.
But for cancer cells to metastasize, they have to leave the primary tumor, travel thru the blood stream, exit at the distant organ, seed there, and then grow.
Leaving the primary site and entering the blood stream is part of a process called Epithelial to Mesenchymal Transition (EMT). Leaving the bloodstream and entering the next tissue is called Mesenchymal to Epithelial Transition. In this video, I’ll walk you thru recent experimental data in the field that points to the importance of how both sides of the transition are necessary for cancer cells to metastasize, and the emerging concept of clusters of circulating tumor cells in the blood that could have mixed properties.
Sources covered:
Phenotypic Heterogeneity and Metastasis of Breast Cancer Cells. Hapach et al. Cancer Research. 2021
Better together: Circulating tumor cell clustering in metastatic cancer. Schuster et al. Trends in Cancer. 2021
Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis. Liu et al. Science Advances. 2019
Epithelial cell division - multiplying without losing touch. Bras & Borgne. Journal of Cell Science. 2014
Epithelial-mesenchymal transition induced by growth suppressor p12 CDK2-AP1 promotes tumor cell local invasion by suppresses distance colony growth. Tsuji et al. Cancer Research. 2008
Metastatic Colonization Requires the Repression of the Epithelial-Mesenchymal Transition Inducer Prrx1. Ocana et al. Cancer Cell. 2012.
Spatiotemporal Regulation of Epithelial-Mesenchymal Transition is Essential for Squamous Cell Carcinoma Metastasis. Tsai et al. Cancer Cell. 2012
Circulating Tumor Cell Clusters are Oligoclonal Precursors of Breast Cancer Metastasis. Aceto et al. Cell. 2014
Detection of clustered circulating tumour cells in early breast cancer. Krol et al. British Journal of Cancer. 2021
Homophilic CD44 Interactions Mediate Tumor Cell Aggregation and Polyclonal Metastasis in Patient-Derived Breast Cancer Models. Liu et al. Cancer Discovery. 2019
Clusters of circulating tumor cells traverse capillary-sized vessels. Au et al. PNAS. 2016
Extracellular fluid viscosity enhances cell migration and cancer dissemination. Bera et al. Nature. 2022.
How the Macrophage Corpse Eating habit convinces them to Ally with Cancer Cells
Efferocytosis: how Cancer Cells use this Macrophage trait to turn them against our own Immune System. In this video, I'll show you how the Macrophage's job: cleaning up dead cell corpses, is opportunistically hijacked by cancer cells to their own advantage.
Literature References in order of appearance:
Dr. David Roger’s Neutrophil Movie, Vanderbilt University
Macrophages lift off surface-bound bacteria using a filopodium-lamellipodium hook-and-shovel mechanism. Moller et al. Scientific Reports. 2013
An estimation of the number of cells in the human body. Ann. Hum. Biol. 40, 463–471 (2013). Bianconi et al. Ann. Hum. Bill. 2013
Phagocytosis of apoptotic cells in homeostasis. Arandjelovic & Ravichandran, Nature Immunology 2015
Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure. Segawa et al. Science 2014
Efferocytosis in health and disease. Doran et al. Nature Reviews 2020
Live cell tracking of macrophage efferocytosis during Drosophila embryo development in vivo . Raymond et al. Science 2022.
Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer . Birge et al. Cell Death and Differentiation 2016.
MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression . Lin et al. Oncoimmunology 2022
Tumor associated macrophages regulate PD-1/PD-L1 immunosuppression. Pu & Ji. Frontiers in Immunology Review 2022.
Cancer immunotherapy using checkpoint blockade. Ribas & Wolchok. Science 2018
Biological activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patents. Hodi et al. PNAS 2003
A decade of immune-checkpoint inhibitors in cancer therapy. Robert. Nature Communications 2020
Durable Complete Response after discontinuation of Pembrolizumab in Patients with Metastatic Melanoma. Robert et al. Journal of Clinical Oncology 2018.
Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers. Hopkins et al. British Journal of Cancer. 2017.
Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors. Bai et al. Biomarker Research 2020
How Macrophages stitch blood vessels to give us life, healing, and cancer
Vascular Anastomosis is the process where Macrophages stitch together endothelial sprouts to give us new blood vessels. This is a necessary biological process during fetal development and wound healing. Yet, this same process also provides a way to feed tumors and for cancer cells to metastasize.
References
Chapter 1: Overview of Angiogenesis. Adair & Montani. Angiogenesis. 2010
Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and repression. Gurevich et al. EMBO. 2018
Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Fantin et al. Blood. 2010
Macrophage regulation of angiogenesis in health and disease. Martin & Gurevich. Seminars in Cell & Dev Bio. 2021
Hif-1a regulates macrophage-endothelial interactions during blood vessel development in zebrafish. Gerri et al. Nat Comm. 2016
4D atlas of the mouse embryo for precise morphological staging. Wong et al. Development. 2015
Macrophages Mediate the Repair of Brain Vascular Rupture through Direct Physical Adhesion and Mechanical Traction. Liu et al. Immunity. 2016
Pioneer neutrophils release chromatin within in vivo swarms. Isles et al. eLife. 2021
In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds. Rodero et al. PLOS One. 2014
Macrophages form functional vascular mimicry channels in vivo. Barnett et al. Scientific Reports. 2016
Real-Time Imaging Reveals Local, Transient Vascular Permeability, and Tumor Cell Intravasation Stimulated by TIE2hi Macrophage-Derived VEGFA
Tumors: Wounds that do not heal. Dvorak. Seminars in Medicine. 1986
The hallmarks of cancer are also the hallmarks of wound healing. MacCarthy-Morrogh & Martin. Science Signaling. 2020
Macrophages as tools and targets in cancer therapy. Mantovani et al. Nature Reviews 2022.
Every discovery is a mystery unfolding in real time.
How would you tell yours?
Feel free to email me at beiyun@cliubioanimation.studio,
and let’s explore some new avenues together!