Molecular flexibility of high molecular weight hyaluronic acid has a profound effect on invasion of cancer cells

Abstract

Hyaluronic acid (HA) is an abundant component of extracellular matrix known to be important in cancer; low molecular weight HA typically correlates with cancer progression, high molecular weight HA with homeostasis. Here we show that even high molecular weight HA can induce cancer cell migration when diluted. We show by NMR spectroscopy that diluted high molecular weight HA molecules can access the conformations needed for strong binding to the primary cell surface receptor for HA, CD44 on the necessary timescale for induction of CD44 signalling. The high dilution HA condition correlates with profound changes in brain cancer cell morphology and proteome which supports cancer cell invasion. We suggest that the flexibility of HA molecules is central to HA-mediated cell signalling rather than its molecular weight.