Complement factor H: a biomarker for progression of cutaneous squamous cell carcinoma

Area of Science:

• Dermatology
• Oncology
• Immunology

Background:

• The global incidence of cutaneous squamous cell carcinoma (cSCC) is rising.
• Understanding the molecular mechanisms driving cSCC progression is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of complement system components in cSCC.
• To identify potential biomarkers and therapeutic targets for cSCC.

Main Methods:

• Expression profiling of cSCC cell lines and normal keratinocytes using Affymetrix and qPCR.
• Immunohistochemical analysis of CFH and FHL-1 expression in cSCC tumors, in situ cSCCs, and actinic keratoses.
• Investigating the regulatory pathways (IFN-γ, ERK1/2, p38) and functional effects (proliferation, migration) of CFH and FHL-1.

Main Results:

• Complement factor H (CFH) and factor H-like protein-1 (FHL-1) were upregulated in cSCC cell lines and tumors compared to normal skin.
• CFH and FHL-1 were specifically expressed by tumor cells in invasive cSCCs, with higher intensity than in in situ cSCCs and actinic keratoses.
• CFH expression was induced by IFN-γ, and basal CFH/FHL-1 expression depended on ERK1/2 and p38 signaling. Knockdown of CFH/FHL-1 inhibited proliferation, migration, and ERK1/2 activation.

Conclusions:

• CFH and FHL-1 are implicated in the progression of cSCC.
• These complement factors serve as potential progression markers and therapeutic targets for skin SCCs.