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During epithelial-to-mesenchymal transition (EMT), cancer cells lose their cell–cell adhesion junctions as they become more metastatic, altering cell motility and focal adhesion disassembly associated with increased detachment from the primary tumor and a migratory response into nearby tissue and vasculature. Current in vitro strategies characterizing a cell's metastatic potential heavily favor quantifying the presence of cell adhesion biomarkers through biochemical analysis; however, mechanical cues such as adhesion and motility directly relate to cell metastatic potential without needing to first identify a cell specific biomarker for a particular type of cancer. This paper presents a comprehensive comparison of two functional metrics of cancer aggression, wound closure migration velocity and cell detachment from a culture surface, for three pairs of epithelial cancer cell lines (breast, endometrium, tongue tissue origins). It was found that one functional metric alone was not sufficient to categorize the cancer cell lines; instead, both metrics were necessary to identify functional trends and accurately place cells on the spectrum of metastasis. On average, cell lines with low metastatic potential (MCF-7, Ishikawa, and Cal-27) were more aggressive through wound closure migration compared to loss of cell adhesion. On the other hand, cell lines with high metastatic potential (MDA-MB-231, KLE, and SCC-25) were on average more aggressive through loss of cell adhesion compared to wound closure migration. This trend was true independent of the tissue type where the cells originated, indicating that there is a relationship between metastatic potential and the predominate type of cancer aggression. Our work presents one of the first combined studies relating cell metastatic potential to functional migration and adhesion metrics across cancer cell lines from selected tissue origins, without needing to identify tissue-specific biomarkers to achieve success. Using functional metrics provides powerful clinical relevancy for future predictive tools of cancer metastasis.
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To seal a wound, caterpillars transform blood from a viscous to a viscoelastic fluid in a few seconds
In insects vulnerable to dehydration, the mechanistic reaction of blood after wounding is rapid. It allows insects to minimize blood loss by sealing the wound and forming primary clots that provide scaffolding for the formation of new tissue. Using nano-rheological magnetic rotational spectroscopy with nickel nanorods and extensional rheology, we studied the properties of blood dripping from the wound of caterpillars of the Carolina sphinx moth (Manduca sexta) with a high concentration of blood cells. We discovered that wound sealing followed a two-step scenario. First, in a few seconds, the Newtonian low-viscosity blood turns into a non-Newtonian viscoelastic fluid that minimizes blood loss by retracting the dripping blood back into the wound. Next, blood cells aggregate, starting from the interfaces and propagating inward. We studied these processes using optical phase-contrast and polarized microscopy, X-ray imaging, and modeling. Comparative analyses of the cell-rich and cell-poor blood of different insects revealed common features of blood behavior. These discoveries can help design fast-working thickeners for vertebrate blood, including human blood.
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- Award ID(s):
- 2042937
- PAR ID:
- 10504793
- Publisher / Repository:
- Frontiers in Soft Matter
- Date Published:
- Journal Name:
- Frontiers in Soft Matter
- Volume:
- 4
- ISSN:
- 2813-0499
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.3389/frsfm.2024.1341129
