Nephronectin promotes breast cancer brain metastatic colonization via its integrin-binding domains.

Scientific Reports
Synnøve Norvoll MagnussenGunbjørg Svineng

Abstract

This study demonstrates a role for the extracellular matrix protein nephronectin (NPNT) in promoting experimental breast cancer brain metastasis, possibly through enhanced binding to- and migration through brain endothelial cells. With the introduction of more targeted breast cancer treatments, a prolonged survival has resulted during the last decade. Consequently, an increased number of patients develop metastasis in the brain, a challenging organ to treat. We recently reported that NPNT was highly expressed in primary breast cancer and associated with unfavourable prognosis. The current study addresses our hypothesis that NPNT promotes brain metastases through its integrin-binding motifs. SAGE-sequencing revealed that NPNT was significantly up-regulated in human breast cancer tissue compared to pair-matched normal breast tissue. Human brain metastatic breast cancers expressed both NPNT and its receptor, integrin α8β1. Using an open access repository; BreastMark, we found a correlation between high NPNT mRNA levels and poor prognosis for patients with the luminal B subtype. The 66cl4 mouse cell line was used for expression of wild-type and mutant NPNT, which is unable to bind α8β1. Using an in vivo model of brain metastatic co...Continue Reading

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Citations

Mar 7, 2021·Cancers·Synnøve Norvoll MagnussenGunbjørg Svineng

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Methods Mentioned

BETA
xenograft
xenografts
Profiler
PCR
scraping

Software Mentioned

BreastMark
Leica Application Suite ( LAS
DESeq2
ImmunoRatio
Proteome Profiler

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