Complement Factor H: A Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Abstract

The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing globally. We have studied the expression of complement system components in cSCC. Expression profiling of cSCC cell lines (n=8) and normal human epidermal keratinocytes (n=5) with Affymetrix and quantitative real-time PCR (qPCR) revealed upregulation of complement factor H (CFH) and factor H-like protein-1 (FHL-1) in cSCC cell lines. The expression of CFH and FHL-1 mRNAs was also significantly higher in cSCC tumors (n=6) than in normal skin (n=11). Analysis of CFH and FHL-1 expression in vivo in invasive cSCCs (n=65), in situ cSCCs (n=38), and premalignant lesions (actinic keratoses, n=37) by immunohistochemistry showed that they were specifically expressed by tumor cells in cSCCs and the staining intensity was stronger in cSCCs than in in situ cSCCs and actinic keratoses. The expression of CFH by cSCC cells was upregulated by IFN-γ and the basal CFH and FHL-1 expression was dependent on extracellular signal-regulated kinase (ERK)1/2 and p38 signaling. Knockdown of CFH and FHL-1 expression inhibited proliferation and migration of cSCC cells and inhibited basal ERK1/2 activation. These results provide evidence for a role of CFH and FHL-1 in cSCC progression and identify them as progression markers and potential therapeutic targets in SCCs of skin.

Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1

“…However, there are no reports that describe how complement proteins C7 and CFH function in TICs, especially for upregulating stemness. A recent report showed that CFH is upregulated in cutaneous squamous cell carcinoma (cSCC), and its knockdown inhibits the proliferation and migration of cSCC cells [25]. In contrast, the role of C7 in cancer cells is still not well understood.…”

From Normal Skin to Squamous Cell Carcinoma: A Quest for Novel Biomarkers

“…Inflammation is involved in many types of pathologies, from AK and Bowen's disease (BD) to cutaneous SCC (cSCC) and other kind of cancers; thus the involvement of inflammatory markers, such as the complement factor H (CFH) and FHL-1 (factor H-like protein-1) in the development of cSCC has attracted an increasing interest [60]. CFH is a soluble molecule that has a role in inhibiting one of the three pathways which activates the complement C3, the alternate pathway (which is continuously activated in vivo ), and it also represents a cofactor for complement factor 1 in the inactivation process of C3b to iC3b [61, 62, 97].…”

In Silico Analysis Validates Proteomic Findings of Formalin-fixed Paraffin Embedded Cutaneous Squamous Cell Carcinoma Tissue

“…The ability to discriminate SCC variants based on distinct molecular profiles is of great importance when assessing the risk of progression, as well as the clinical management, of patients with cSCC (13). While immunohistochemistry and western blot studies have identified several abundant proteins differentially expressed between cSCC, actinic keratosis (AK) and Bowen's disease lesions, including cyclin-dependent kinase inhibitor 1B (p27), TP53 (14)(15)(16), serpin A1 (SERPINA1) (17); matrix metalloproteinase (MMP)-2, -7, -9 and -13 (16,18,19); c-myc protein (C-MYC) (20); tenascin-C (TNC) (21); and complement factor-I (CFI) and complement factor-H (CFH) (22,23), these markers have not been useful for classifying cSCC subtypes into clinically meaningful categories. The need for comprehensive molecular profiling of cSCC is clear (24).…”