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Micrograph of a region of zebrafish skin where a track of cancer cells has disrupted the epithelium much like a mole burrowing beneath a lawn of grbad. Credit: University of Bristol
Cancer-related inflammation impacts significantly on cancer development and progression. New research has been observed in zebrafish, for the first time, that inflammatory cells use weak spots or micro-perforations in the extracellular matrix barrier to access skin cancer cells.
The research, led by the University of Bristol and published in Cell Reports today [Tuesday 4 June], used translucent zebrafish to model several spells of skin cancer and live image To access the cancer cells, the immune cells need to be broken down into an extracellular matrix barrier called the basement membrane zone.
The researchers observed weak spots in the basement membrane area, which the inflammatory cells use as easy routes to cancer access. Those clones of cancer cells are more likely to grow as they grow faster.
Paul Martin, Professor of Cell Biology in the Schools of Biochemistry and Physiology, Pharmacology & Neuroscience at the University of Bristol, said: "As the zebrafish are translucent, we can watch inflammatory cells interacting with cancer in their own tissues. .
"This 'window' on the cancer process has revealed 'weak spots' in the barrier layer of inflammatory cells that need to be broken in. Now we know these micro-perforations exist we can target them with cancer therapeutics. "
Inflammatory cells (white blood cells) are known to be key players promoting cancer malignancy from the earliest stages of cancer initiation, but it has been unclear how they gain access to the cancer cells which generally develop epithelial tissues, which has a barrier layer of extracellular matrix between them and the tissues from where the inflammatory cells arise. Inflammatory cells could kill the growing cancer but instead tend to nourish it and encourage cancer progression.
The study 's findings have been clearly linked to cancer patients because they have been shown to be very similar in the way they have been shown to occur in humans and to prevent cancer.
Reference: Maaike C. W. van den Berg, et al. Proteolytic and Opportunistic Breaching of the Basement Membrane Zone by Immune Cells during Tumor Initiation. Cell Reports (2019) DOI: https://doi.org/10.1016/j.celrep.2019.05.029
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