Proteomics

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Temporal multi-omics identifies LRG1 as vascular instructor of early metastatic colonization.

ABSTRACT: Metastasis is the primary cause of cancer-related mortality and the mechanistically least well understood step of the tumor progression cascade. Employing surgical preclinical metastasis models, we show here that small primary tumors reprogram the body’s vascular endothelium to alter systemic homeostasis and to condition the premetastatic niche for metastatic colonization. Endothelial cells thereby serve as an amplifier of tumor-induced instructive signals. The combined endothelial transcriptomic and serum proteomic screen identified the TGFß pathway signaling specifier LRG1 as an early vascular niche instructor of metastatic colonization. Adjuvant LRG1 inhibition to primary tumor-resected mice delayed metastatic growth and increased overall survival. The study has thereby established the premetastatic systems map of primary tumor-induced vascular changes and identified LRG1 as a therapeutic target for metastasis

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Bianca Kuhn  

LAB HEAD: Prof. Dr. Hellmut Augustin

PROVIDER: PXD013978 | Pride | 2022-05-16

REPOSITORIES: Pride

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Metastasis is the primary cause of cancer-related mortality. Tumor cell interactions with cells of the vessel wall are decisive and potentially rate-limiting for metastasis. The molecular nature of this cross-talk is, beyond candidate gene approaches, hitherto poorly understood. Using endothelial cell (EC) bulk and single-cell transcriptomics in combination with serum proteomics, we traced the evolution of the metastatic vascular niche in surgical models of lung metastasis. Temporal multiomics r  ...[more]

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