Autologous Paracrine Prostasin-Matriptase Serine Protease Interaction in Lymphoid Cancer Cells

Area of Science:

• Biochemistry
• Cell Biology
• Oncology

Background:

• Prostasin, a serine protease on exosome surfaces, interacts with matriptase, a serine protease over-expressed on cancerous B cells.
• This interaction initiates a proteolytic cascade, leading to matriptase activation, self-activation, and subsequent removal from cancer cells, thereby reducing proliferation and migration.

Purpose of the Study:

• To test if prostasin can remove matriptase from lymphoid cells via activation and self-activation.
• To investigate the potential of using genetically engineered autologous cells expressing prostasin for therapeutic purposes.

Main Methods:

• Co-culture experiments using prostasin-positive and prostasin-negative cells.
• Flow cytometry to quantify matriptase removal.
• In silico analysis of RNA-seq profiles from B-cell lymphoma patients.
• Flow cytometry to assess prostasin's impact on cluster of differentiation molecules in peripheral blood mononuclear cells.

Main Results:

• Matriptase was dose-dependently removed from prostasin-negative cells when co-cultured with prostasin-positive cells.
• The paracrine removal of matriptase required the active sites of both prostasin and matriptase.
• B-cell lymphoma patient samples showed imbalanced expression of matriptase, prostasin, and their inhibitors.
• Exosomal prostasin influenced cluster of differentiation molecules in activated human peripheral blood mononuclear cells, suggesting a role in adaptive immunity regulation.

Conclusions:

• The prostasin-matriptase interaction is a viable autologous paracrine mechanism for removing excess matriptase.
• This interaction can be leveraged to target diseases characterized by over-expressed matriptase, such as B-cell lymphoma.
• Prostasin may play a role in regulating cellular adaptive immunity.