Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Poster Abstracts

6-POS Board 6 CD44-HA INTERACTION MEDIATES FAST CELL MOTILITY Swetlana Ghosh 1 ; 1 IIT Bombay, Biosciences & Bioengineering, Mumbai, India

The extracellular matrix (ECM) is a dense network comprising structural proteins (e.g., collagen), glycoproteins (e.g., mucins), and proteoglycans (e.g., hyaluronic acid, HA). Elevated levels of collagen and HA are frequently observed in various cancers. Cancer cells secrete increased amounts of matrix metalloproteinases (MMPs), particularly MMP-9, which remodel the ECM and facilitate metastasis. MMP-9 can bind to CD44, a principal HA receptor on the cell surface, yet the functional significance of the CD44–MMP-9 interaction within HA-rich ECM remains unclear. To examine the combined contribution of HA–CD44 engagement and MMP-9–mediated invasion, we engineered collagen–HA gels that replicate key features of the in vivo ECM. By varying the collagen-HA ratio, we found that increasing HA content enhances plasticity of the hydrogels, reduces cell spreading, and accelerates cell migration. Notably, knockout of CD44 abolished the HA-induced increase in migration, demonstrating the essential role for CD44 owing to this effect. In summary, our findings reveal that HA-driven changes in ECM mechanics, combined with CD44–HA interactions, significantly promote cancer cell migration—likely through enhanced MMP-9 activity. These results highlight the dual importance of matrix plasticity and CD44 engagement in regulating MMP-9–dependent invasion.

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