C5aR1 Promotes Invasion, Metastasis, and Poor Prognosis in Cutaneous Squamous Cell Carcinoma

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a prevalent metastatic skin cancer with a poor prognosis.
• The role of the complement system, specifically C5a receptor 1 (C5aR1), in cSCC progression and metastasis is not well understood.

Purpose of the Study:

• To investigate the expression and function of C5aR1 in the development and metastasis of cSCC.
• To evaluate C5aR1 as a potential biomarker for metastatic risk and patient survival in cSCC.

Main Methods:

• Utilized a three-dimensional spheroid co-culture model with fibroblasts and recombinant C5a treatment.
• Analyzed C5aR1 expression in human cSCC xenografts, primary cSCCs, premalignant lesions, and normal skin using multiplex immunofluorescence and immunohistochemistry.

Main Results:

• C5aR1 expression was upregulated in cSCC cells co-cultured with fibroblasts, and C5a enhanced cSCC cell invasion.
• Elevated C5aR1 was found on tumor cells and fibroblasts in invasive cSCCs, including those associated with recessive dystrophic epidermolysis bullosa.
• Increased C5aR1 expression correlated with higher metastatic risk and poorer disease-specific survival in patients with primary cSCC.

Conclusions:

• C5a signaling contributes to cSCC cell invasion.
• C5aR1 serves as a novel biomarker for predicting metastasis risk and prognosis in cSCC patients.
• C5aR1 represents a potential therapeutic target for locally advanced and metastatic cSCC.