A novel role of low molecular weight hyaluronan in breast cancer metastasis

Abstract

Low molecular weight hyaluronan (LMW‐HA), a degradation fragment of the extracellular matrix component hyaluronan (HA), has been proven to play a crucial role in cancer progression. However, no systematic clinical study of breast cancer has been performed to correlate LMW‐HA levels with metastasis. In the present study, we analyzed 176 serum specimens and found for the first time that the serum LMW‐HA (but not total HA) level significantly correlated with lymph node metastasis, suggesting that serum LMW‐HA represents a better prognostic indicator of breast cancer progression than HA. Similarly, we found that breast cancer cell lines displaying higher invasive potential had a higher LMW‐HA concentration than less‐invasive cell lines. This higher LMW‐HA level was accompanied by the overexpression of hyaluronan synthase (HAS2) and hyaluronidase (both HYAL1 and HYAL2). Of great importance, decreasing LMW‐HA production significantly inhibited breast cancer cell migration and invasion. Overall, our results suggest that during cancer progression, cancer cells may actively remodel their microenvironment via an autocrine/paracrine‐like process, resulting in elevated LMW‐HA levels, which in turn may facilitate cancer progression by promoting the migration and invasion of cancer cells. Therefore, cancer‐associated LMW‐HA may be a more promising molecular biomarker than total HA for detecting metastasis and may have further applications in breast cancer treatment.—Wu, M., Cao, M., He, Y., Liu, Y., Yang, C., Du, Y., Wang, W., Gao, F. A novel role of low molecular weight hyaluronan in breast cancer metastasis. FASEB J. 29, 1290‐1298 (2015). www.fasebj.org