Fragmented hyaluronan is an autocrine factor potentiating cancer cell invasion supported by HAS2 -CD44/hyaluronidase-2 system on the plasma membrane

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Here we show that fragmented 23 kDa HA elicits enhanced cell motility and changes the shape of epithelial cells. Our study also indicates that hyaluronidase-2-mediated catabolism could play a significant role in the generation of LMWHA (about 20 kDa) with the association of CD44 in epithelial cells. This indicates the possibility that fragmented HA acts as a mediator in the autocrine/paracrine mechanism. Our study showed that signals initiated by LMWHA-CD44 interactions induce the phenotypes of cancer cells undergoing epithelial-mesenchymal transition (EMT), expanding our understanding of the functions of HA in cancer cell biology.