[The metalloproteinases in cancer]

Area of Science:

• Oncology
• Biochemistry
• Molecular Biology

Background:

• Matrix metalloproteinases (MMPs) and serine proteases are crucial in tumor-associated tissue remodeling.
• Protease inhibitors were historically considered direct anti-cancer agents.
• Recent advancements in genomics and transgenesis have refined our understanding of proteolysis in cancer.

Discussion:

• Tumorigenesis involves complex proteolytic processes, with proteases and their inhibitors playing multifaceted roles.
• Contrary to initial beliefs, host cells, rather than tumor cells, are significant producers of these enzymes in the peritumoral environment.
• The genome stability of host cells presents an advantage over inherently unstable cancer cell genomes.

Key Insights:

• Host cells actively participate in cancer progression by producing key proteases and inhibitors.
• Proteases exhibit multifunctionality, regulating critical cancer hallmarks like growth, angiogenesis, and invasion.
• The peritumoral proteolytic system, orchestrated by host cells, represents a novel therapeutic avenue.

Outlook:

• Targeting host cell-derived proteases offers a promising strategy for cancer therapy.
• Further research into the specific mechanisms of host cell proteolysis in cancer is warranted.
• Exploiting the genomic stability of host cells could lead to more effective and less toxic cancer treatments.