Article: Sialyl Lewisx-P-selectin cascade mediates tumor–mesothelial adhesion in ascitic fluid shear flow

TitleSialyl Lewisx-P-selectin cascade mediates tumor–mesothelial adhesion in ascitic fluid shear flow
Authors
Issue Date2019
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2019, v. 10, article no. 2406 How to Cite?
AbstractOrgan-specific colonization suggests that specific cell–cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). We show that the M-CSCs tether more and roll slower than the non-metastatic (NM)-CSCs, thus resulting in the preferential binding to the peritoneal mesothelium under ascitic fluid shear stress. Mechanistically, this interaction is mediated by P-selectin expressed by the peritoneal mesothelium. Insulin-like growth factor receptor-1 carrying an uncommon non-sulfated sialyl-Lewisx (sLex) epitope serves as a distinct P-selectin binding determinant. Several glycosyltransferases, particularly α1,3-fucosyltransferase with rate-limiting activity for sLex synthesis, are highly expressed in M-CSCs. Tumor xenografts and clinical samples corroborate the relevance of these findings. These data advance our understanding on the molecular regulation of peritoneal metastasis and support the therapeutic potential of targeting the sLex-P-selectin cascade.
Persistent Identifierhttp://hdl.handle.net/10722/271320
ISSN
2017 Impact Factor: 12.353
2015 SCImago Journal Rankings: 6.539
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLi, SS-
dc.contributor.authorIp, CKM-
dc.contributor.authorTang, MYH-
dc.contributor.authorTang, MKS-
dc.contributor.authorTong, Y-
dc.contributor.authorZhang, J-
dc.contributor.authorHassan, AA-
dc.contributor.authorMak, ASC-
dc.contributor.authorYung, SSY-
dc.contributor.authorChan, TM-
dc.contributor.authorIp, PP-
dc.contributor.authorLee, CL-
dc.contributor.authorChiu, CN-
dc.contributor.authorLee, LTO-
dc.contributor.authorLai, HC-
dc.contributor.authorZeng, JZ-
dc.contributor.authorShum, HC-
dc.contributor.authorWong, AST-
dc.date.accessioned2019-06-24T01:07:34Z-
dc.date.available2019-06-24T01:07:34Z-
dc.date.issued2019-
dc.identifier.citationNature Communications, 2019, v. 10, article no. 2406-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/271320-
dc.description.abstractOrgan-specific colonization suggests that specific cell–cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). We show that the M-CSCs tether more and roll slower than the non-metastatic (NM)-CSCs, thus resulting in the preferential binding to the peritoneal mesothelium under ascitic fluid shear stress. Mechanistically, this interaction is mediated by P-selectin expressed by the peritoneal mesothelium. Insulin-like growth factor receptor-1 carrying an uncommon non-sulfated sialyl-Lewisx (sLex) epitope serves as a distinct P-selectin binding determinant. Several glycosyltransferases, particularly α1,3-fucosyltransferase with rate-limiting activity for sLex synthesis, are highly expressed in M-CSCs. Tumor xenografts and clinical samples corroborate the relevance of these findings. These data advance our understanding on the molecular regulation of peritoneal metastasis and support the therapeutic potential of targeting the sLex-P-selectin cascade.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject.meshAnimals-
dc.subject.meshAscitic Fluid-
dc.subject.meshCarcinoma/metabolism-
dc.subject.meshCarcinoma/secondary-
dc.subject.meshCell Adhesion-
dc.titleSialyl Lewisx-P-selectin cascade mediates tumor–mesothelial adhesion in ascitic fluid shear flow-
dc.typeArticle-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.emailYung, SSY: ssyyung@hku.hk-
dc.identifier.emailChan, TM: dtmchan@hku.hk-
dc.identifier.emailIp, PP: philipip@hku.hk-
dc.identifier.emailLee, CL: h0003053@hkusua.hku.hk-
dc.identifier.emailChiu, CN: pchiucn@hku.hk-
dc.identifier.emailShum, HC: ashum@hku.hk-
dc.identifier.emailWong, AST: awong1@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.identifier.authorityYung, SSY=rp00455-
dc.identifier.authorityChan, TM=rp00394-
dc.identifier.authorityIp, PP=rp01890-
dc.identifier.authorityLee, CL=rp02515-
dc.identifier.authorityChiu, CN=rp00424-
dc.identifier.authorityShum, HC=rp01439-
dc.identifier.authorityWong, AST=rp00805-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-019-10334-6-
dc.identifier.pmid31160622-
dc.identifier.pmcidPMC6547673-
dc.identifier.scopuseid_2-s2.0-85066616189-
dc.identifier.hkuros298247-
dc.identifier.hkuros300448-
dc.identifier.volume10-
dc.identifier.spagearticle no. 2406-
dc.identifier.epagearticle no. 2406-
dc.publisher.placeUnited Kingdom-

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