# Activated platelet-derived exosomal LRG1 promotes multiple myeloma cell growth

## TL;DR

This study shows that platelet-derived exosomal LRG1 promotes multiple myeloma cell growth and worsens patient outcomes.

## Contribution

The novel finding is that LRG1 in platelet exosomes drives MM progression via EMT and angiogenesis, offering a new therapeutic target.

## Key findings

- Platelet-derived exosomal LRG1 promotes MM cell proliferation and reduces apoptosis.
- Blocking LRG1 eliminates the growth-promoting effect of exosomes on MM cells.
- High exosomal LRG1 levels correlate with poor prognosis in MM patients.

## Abstract

The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.