Lin deceasing brain molecules could prevent harmful cancer spread
In a groundbreaking study published in Royal Society Open Science, researchers led by Melinda Duer, a Fellow of Robinson College, Cambridge, have uncovered new insights into the role of hyaluronic acid (HA) in cancer recurrence after primary surgery. The study, titled "Molecular flexibility of hyaluronic acid has a profound effect on invasion of cancer cells," received support from the European Research Council, the Engineering and Physical Sciences Research Council (EPSRC), and UK Research and Innovation (UKRI).
The research team hypothesises that the flexibility of HA molecules is central to HA-mediated cell signaling. They found that even high-molecular-weight HA can induce cancer cell migration when it is highly diluted. This surprising discovery challenges the conventional understanding that only low-molecular-weight HA can facilitate cell migration.
At higher concentrations, high-molecular-weight HA molecules have insufficient flexibility for strong CD44 binding, the primary receptor for HA-induced cell signaling. However, under high dilution conditions, these molecules are able to access the conformations needed for strong binding to CD44 on the tens of nanosecond time scale. This binding leads to profound changes in brain cancer cell morphology and proteome, supporting cancer cell invasion.
The study also revealed that the high dilution HA condition correlates with changes that support cancer cell invasion. These changes include the reorganisation of the cytoskeleton, alterations in gene expression, and the activation of signaling pathways known to promote cancer cell migration and invasion.
While this study was conducted in Cambridge, another research team at the National University of Singapore (NUS) is working on a different approach to stop the spread of glioblastoma by refreezing hyaluronic acid. Both studies underscore the importance of understanding the role of hyaluronic acid in cancer recurrence and metastasis, and open up new avenues for developing targeted therapies to combat this devastating disease.
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