MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Matrix metalloproteinase MMP-9 (gelatinase B) is implicated in skin cancer progression.
• Its role in multi-stage epidermal tumorigenesis induced by HPV16 oncogenes requires further elucidation.

Purpose of the Study:

• To investigate the specific contributions of MMP-9 to squamous carcinogenesis in a mouse model.
• To determine the cellular sources of MMP-9 involved in tumor development.

Main Methods:

• Utilized transgenic mice lacking MMP-9 and HPV16 oncogenes.
• Employed bone marrow transplantation to create chimeric mice with selective MMP-9 expression in hematopoietic cells.
• Analyzed keratinocyte proliferation, differentiation, and tumor invasion.

Main Results:

• Mice lacking MMP-9 exhibited reduced keratinocyte hyperproliferation and fewer invasive tumors.
• Carcinomas in MMP-9-deficient mice showed greater loss of differentiation, indicating higher grade and more aggressive tumors.
• MMP-9 was primarily expressed in inflammatory cells (neutrophils, macrophages, mast cells), not neoplastic cells.
• Hematopoietic MMP-9 expression was sufficient to drive MMP-9-dependent carcinogenesis.

Conclusions:

• MMP-9 plays a dual role in skin carcinogenesis, promoting proliferation but also potentially limiting tumor aggressiveness.
• Inflammatory cells, through MMP-9 production, act as key contributors to squamous carcinogenesis.