Dataset Information

Lyve-1 deficiency plasma proteomics

ABSTRACT: Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding hyaluronan, LYVE-1 mediates adhesion of leukocytes and cancer cells to endothelial cells. Here, we analyzed the impact of LYVE-1 on physiological liver functions and metastasis. Mice with deficiency of Lyve-1 (Lyve-1 KO) were analyzed using histology, immunofluorescence, RNA sequencing, plasma proteomics and flow cytometry. Liver metastasis was studied by intrasplenic/intravenous injection of melanoma (B16F10luc2, WT31) or colorectal carcinoma (MC38) cell lines. Results: Hepatic architecture, liver size, endothelial differentiation and angiocrine functions were unaltered in Lyve-1 KO mice. Hyaluronan plasma levels were significantly increased in Lyve-1-KO mice; besides, plasma proteomics revealed increased carbonic anhydrase-2 and decreased FXIIIA, potential modulators of metastatis. Furthermore, gene expression analysis of LSEC indicated regulation of immunological pathways. Therefore, liver metastasis of a highly and of a weekly immunogenic tumor, i.e. melanoma and colorectal carcinoma (CRC), was analyzed in Lyve-1 KO mice. Hepatic metastasis of B16F10 luc2 and WT31 melanoma cells, but not MC38 CRC cells, was significantly reduced in Lyve-1 KO mice. While short-term adhesion assays with B16F10 luc2 cells in vivo did not show differences between Lyve-1 KO and wild-type mice, increased numbers of resident hepatic CD4+, CD8+ and regulatory T cells were detected in Lyve-1 KO livers. In addition, iron deposition was detected in F4/80+ liver macrophages known to exert pro-inflammatory effects. Conclusions: LYVE-1 deficiency controlled hepatic metastasis in a tumor cell-specific manner reducing hepatic metastasis of melanoma, but not CRC. Anti-tumorigenic effects are likely due to enhancement of the resident hepatic immune microenvironment.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Hendrik Nolte

LAB HEAD: Hendrik Nolte

PROVIDER: PXD032717 | Pride | 2023-03-11

REPOSITORIES: Pride

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			Action	DRS
	20210917_HN_0137_ThLeKO_LYVE_sample_63.raw	Raw
	20210917_HN_0137_ThLeKO_LYVE_sample_64.raw	Raw
	20210917_HN_0137_ThLeKO_LYVE_sample_65.raw	Raw
	20210917_HN_0137_ThLeKO_LYVE_sample_66.raw	Raw
	20210917_HN_0137_ThLeKO_LYVE_sample_67.raw	Raw

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Publications

Lyve-1 deficiency enhances the hepatic immune microenvironment entailing altered susceptibility to melanoma liver metastasis.

Jauch Anna Sophia AS Wohlfeil Sebastian A SA Weller Céline C Dietsch Bianca B Häfele Verena V Stojanovic Ana A Kittel Maximilian M Nolte Hendrik H Cerwenka Adelheid A Neumaier Michael M Schledzewski Kai K Sticht Carsten C Reiners-Koch Philipp-Sebastian PS Goerdt Sergij S Géraud Cyrill C

Cancer cell international 20221210 1

<h4>Background</h4>Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding to hyaluronan, LYVE-1 can mediate adhesion of leukocytes and cancer cells to endothelial cells. Here, we assessed the impact of LYVE-1 on physiological liver functions and metastasis.<h4>Methods</h4>Mice with deficiency of Lyve-1 (Lyve-1-KO) were analyzed using histology, immunofluorescence, microarray analysis, plasma p ...[more]

PMID: 36496412

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