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FASEB J. 2015 Apr;29(4):1290-8. doi: 10.1096/fj.14-259978. Epub 2014 Dec 30.

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

Author information

1
*Department of Molecular Biology, Department of Rehabilitation Medicine, and Department of Molecular Biology and Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
2
*Department of Molecular Biology, Department of Rehabilitation Medicine, and Department of Molecular Biology and Clinical Laboratory, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China gao3507@126.com.

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.

KEYWORDS:

LMW-HA; biomarker; lymphatic invasion; mammary carcinoma; prognosis

PMID:
25550464
DOI:
10.1096/fj.14-259978
[Indexed for MEDLINE]

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