title: Hyaluroan-regulated lymphatic permeability through S1P receptors is crucial for cancer metastasis.
abstract: Disruption of cancer lymphatic vessel barrier function occurs has been reported to involve in cancer lymphatic metastasis. Hyaluronan (HA), a major glycosaminoglycan component of the extracellular matrix, is associated with cancer metastasis. We investigated the effect of high/low molecular weight hyaluronan (HMW-HA/LMW-HA) on regulation of barrier function and tight junctions in cancer lymphatic endothelial cell (LEC) monolayer. Results showed that LMW-HA increased the permeability of cancer LEC monolayers and induced disruption of Zonula Occludens-1 (ZO-1)-mediated intercellular tight junction and actin stress fiber formation. HMW-HA treatment decreased permeability in cancer LEC monolayers and cortical actin ring formation. As reported, sphingosine 1-phosphate (S1P) receptors are involved in vascular integrity. After silencing of lymphatic vessel endothelial hyaluronan receptor (LYVE-1), upregulation of S1P receptors (S1P1 and S1P3) induced by HMW-HA/LMW-HA were inhibited, respectively. With S1P3 silenced, the disruption of ZO-1 as well as stress fiber formation and the ROCK1/RhoA signaling pathway induced by LMW-HA was not observed in cancer LEC. These results suggested that S1P receptors may play an important role in HMW-HA-/LMW-HA-mediated regulation of cancer lymphatic vessel integrity, which might be the initial step of cancer lymphatic metastasis and a useful intervention of cancer progression.
authors.affiliation: Department of Molecular Biology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
authors.forename: Mengsi
authors.initials: M
authors.lastname: Yu
authors.forename: Pingqing
authors.initials: P
authors.lastname: He
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.forename: Man
authors.initials: M
authors.lastname: Wu
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*; D010539:Permeability; D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D019108:Tight Junctions; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D006820:Hyaluronic Acid