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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.