title: 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.
authors.affiliation: *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.
authors.forename: Man
authors.initials: M
authors.lastname: Wu
authors.affiliation: *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.
authors.forename: Manlin
authors.initials: M
authors.lastname: Cao
authors.affiliation: *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.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.affiliation: *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.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: *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.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.affiliation: *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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.affiliation: *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.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: *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.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D008875:Middle Aged; D008970:Molecular Weight; D009361:Neoplasm Invasiveness; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D006820:Hyaluronic Acid; D051548:Histone Acetyltransferases; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; C115866:OGA protein, human; C473096:Hyal2 protein, human; D006821:Hyaluronoglucosaminidase
keywords: LMW-HA; biomarker; lymphatic invasion; mammary carcinoma; prognosis