Kris Kilian: How Microconstrictions Influence Circulating Melanoma Cells
Kris Kilian, Co-Founder and Chief Scientific Adviser at OxyLo, shared a post on LinkedIn:
“The role of biophysical forces in regulating cell state plasticity continues to be fascinating to me. In our most recent work, Giulia Silvani designed a microfluidic chip to explore how microconstrictions influence circulating melanoma cells and discovered that squeezing through narrow constrictions led to adoption of a tumorigenic phenotype.
Digging deeper into mechanism found that the mechanosensor PIEZO1 is at the heart of this effect. Stimulating PIEZO1 activity increased expression of molecular markers of “stemness”, while inhibition or knockdown abrogated this constriction-induced effect. A custom microfluidic model of extravasation shows that these squeezed cells are primed to engage the endothelium and invade.
Our study adds to the growing body of work relating mechanotransduction of circulating tumour cells to invasive characteristics, with new evidence for tumour forming capacity and organotropism. Ongoing work in the lab suggests this effect is not exclusive to melanoma and that other cancer cell types will adopt tumorigenic traits after constriction.
These results are exciting from a fundamental perspective, but we hope they might also aid prognosis, e.g. assessing metastatic potential in patient-derived material, and drug development efforts, where dynamic phenotype changes during circulation could be studied and targeted.
Finally, with global shifts to using new approach methodologies (NAMs) to supplement/replace animal models, we believe this class of device may be helpful in mimicking metastatic processes in vitro, so that we can more easily develop treatments that target phenotype plasticity to stop the spread of cancer. Thanks to all co-authors for their invaluable contributions and the National Cancer Institute (NCI) and National Health and Medical Research Council (NHMRC) for funding support.”
Title: Capillary constrictions prime cancer cell tumorigenicity through PIEZO1
Authors: Giulia Silvani, Chantal Kopecky, Sara Romanazzo, Vanina Rodríguez, Ayan Das, Elvis Pandzic, John G. Lock, Christine L. Chaffer, Kate Poole, Kristopher A. Kilian
Read The Full Article at Nature Communications.
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