Response of SCC-12F, a human squamous cell carcinoma cell line, to complement attack

Area of Science:

• Immunology
• Cell Biology
• Dermatology

Background:

• The human complement system plays a crucial role in innate immunity but can cause damage to host cells.
• Squamous cell carcinoma (SCC) is a common skin cancer, and its interaction with the complement system is not fully understood.
• Complement regulatory proteins (CRPs) like CD59 and decay-accelerating factor (DAF) are vital for preventing self-damage by complement.

Purpose of the Study:

• To investigate the response of a human SCC cell line (SCC-12F) to complement attack.
• To determine the role of CD59 and DAF in SCC-12F resistance to complement-mediated lysis.
• To identify other cellular responses of SCC-12F to complement, beyond lysis.

Main Methods:

• Utilized a human squamous cell carcinoma cell line (SCC-12F).
• Applied human complement to SCC-12F cells and assessed cell lysis.
• Treated cells with phosphatidylinositol-specific phospholipase C (PIPLC) to remove lipid-linked CRPs (CD59, DAF).
• Quantified complement deposition (C3, C5b-9) and measured prostaglandin F2alpha (PGF2alpha) production.

Main Results:

• SCC-12F cells demonstrated complete resistance to complement-mediated lysis.
• Significant deposition of C3 and C5b-9 was observed on untreated SCC-12F cells.
• Removal of CD59 and DAF increased C3b and C5b-9 deposition and slightly increased cell death.
• Complement attack induced SCC-12F cells to release membrane vesicles containing terminal complement proteins.
• Complement also stimulated SCC-12F cells to produce significant amounts of PGF2alpha.

Conclusions:

• CD59 and DAF are critical for the resistance of SCC-12F cells to complement lysis.
• SCC-12F cells exhibit complement-induced responses including membrane vesicle release and PGF2alpha production.
• These non-lytic responses to complement may contribute to the pathogenesis of inflammatory skin diseases where complement is deposited.