# Autologous Paracrine Prostasin–Matriptase Serine Protease Interaction in Lymphoid Cancer Cells

## TL;DR

This study explores how prostasin from exosomes can activate and remove matriptase on cancerous B cells, potentially offering a new approach for treating B-cell lymphoma.

## Contribution

The study introduces a novel autologous paracrine mechanism using prostasin to target over-expressed matriptase in lymphoid cancer cells.

## Key findings

- Prostasin from exosomes can remove matriptase on cancer cells in a dose-dependent manner.
- The paracrine effect requires the active sites of both prostasin and matriptase.
- RNA-seq analysis shows imbalanced expression of matriptase and prostasin in B-cell lymphoma patient samples.

## Abstract

The serine protease prostasin on the surface of the exosomes released from epithelial cells can interact with ectopically over-expressed cell-surface serine protease matriptase in cancerous B cells to initiate the prostasin–matriptase proteolytic activation cascade. Matriptase activation and the ensuing self-activation result in its removal from cancer cells, reducing cell proliferation and migration. In this study, we tested the hypothesis that the matriptase in the lymphoid cells could be removed by the prostasin-initiated activation and self-activation using genetically engineered autologous cells carrying prostasin. In co-cultures with the prostasin-positive cells, the matriptase on the prostasin-negative vector-control cells was removed in a dose-dependent manner, as determined by flow cytometry. This paracrine phenotype requires the active sites of both proteases. In silico analysis of the RNA-seq profiles indicated an imbalanced expression of high matriptase and low prostasin, and their cognate protease inhibitors in B-cell lymphoma patient specimens. The impact of exosomal prostasin on the cluster of differentiation molecules in activated human peripheral blood mononuclear cells was investigated by flow cytometry, revealing candidate mechanisms for prostasin’s role in regulating cellular adaptive immunity. This autologous paracrine prostasin–matriptase interaction could be exploited as a method for targeting over-expressed matriptase in diseases such as B-cell lymphoma.