Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

Abstract

The incidence of keratinocyte-derived nonmelanoma skin cancers is increasing worldwide because of cumulative recreational exposure to sunlight. At present, no specific molecular markers are available for assessing the progression of premalignant actinic keratoses to invasive cutaneous squamous cell carcinoma (SCC). We examined the role of the Serpin family in skin SCCs. Expression profiling of cutaneous SCC cell lines (n ‫؍‬ 8) revealed up-regulation of SerpinA1 compared with normal epidermal keratinocytes (n ‫؍‬ 5). Analysis with quantitative RT-PCR showed that the mean level of SerpinA1 mRNA was markedly up-regulated in cutaneous SCC cell lines (n ‫؍‬ 8) compared with in normal keratinocytes. SerpinA1 production by SCC cells was dependent on p38 mitogen-activated protein kinase activity and was upregulated by epidermal growth factor, tumor necrosis factor-␣, interferon-␥, and IL-1␤. Immunostaining of tissue arrays with 148 human tissue samples revealed tumor cell-associated expression of SerpinA1 in 19 of 36 actinic keratoses, 22 of 29 Bowen's disease samples, 67 of 71 sporadic SCCs, and all 12 recessive dystrophic epidermolysis bullosa-associated SCCs examined. Moreover, tumor cell-associated SerpinA1 staining was detected in all chemically induced mouse skin SCCs studied (n ‫؍‬ 17). Overexpression of SerpinA1 mRNA was also detected by quantitative RT-PCR in chemically induced mouse skin SCCs (n ‫؍‬ 14) compared with control tissues (n ‫؍‬ 14). These data identify SerpinA1 as a novel tumor cell-associated biomarker for progression of cutaneous SCCs.

p53-Regulated Long Noncoding RNA PRECSIT Promotes Progression of Cutaneous Squamous Cell Carcinoma via STAT3 Signaling

“…10,13 Currently, there is a need for clinically useful biomarkers for predicting the risk of recurrence and metastasis of primary cSCC. Many potential markers have been identified, including inflammation-related complement system proteins, 14e16 PD-L1, 17 Serpin A1, 18 EphB2, 19 AIM2, 20 and P300/CBPassociated factor (PCAF). 21 The authors have previously elucidated the mechanistic role of lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA) in cSCC.…”

Collagens XV and XVIII show different expression and localisation in cutaneous squamous cell carcinoma: type XV appears in tumor stroma, while XVIII becomes upregulated in tumor cells and lost from microvessels

“…Human cSCC cell lines ( n = 8) were established from surgically removed cSCCs . NHEK cultures were established from normal skin of patients ( n = 4) undergoing surgery for mammoplasty , or purchased from PromoCell ( n = 1) (Heidelberg, Germany).…”

“…Human cSCC cell lines ( n = 8) were established from surgically removed cSCCs . NHEK cultures were established from normal skin of patients ( n = 4) undergoing surgery for mammoplasty , or purchased from PromoCell ( n = 1) (Heidelberg, Germany). The spontaneously immortalised non‐tumorigenic human keratinocyte–derived cell line (HaCaT) and three Ha‐ ras ‐transformed tumorigenic HaCaT cell lines (A5, II‐4 and RT3) were kindly provided by Dr Norbert Fusenig (Deutsche Krebsforschungszentrum, Heidelberg, Germany).…”

Podoplanin expression in cutaneous head and neck squamous cell carcinoma—prognostic value and clinicopathologic implications

“…However, key factors determining the risk remain unclear as to 30% of the patients with regional metastatic and recurrent disease do not have an identifiable risk factor 15. Study results suggest that apart from clinicopathologic factors molecular features of the tumor play an essential role in determining the aggressiveness of the tumor 16–18.…”