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A novel role of low molecular weight hyaluronan in breast cancer metastasis
Author(s) -
Wu Man,
Cao Manlin,
He Yiqing,
Liu Yiwen,
Yang Cuixia,
Du Yan,
Wang Wenjuan,
Gao Feng
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-259978
Subject(s) - breast cancer , metastasis , cancer , cancer research , autocrine signalling , paracrine signalling , hyaluronidase , cancer cell , extracellular matrix , hyaluronan synthase , hyaluronic acid , medicine , biology , enzyme , microbiology and biotechnology , biochemistry , receptor , anatomy
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