Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma
Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma
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DOI：
10.1016/j.ajpath.2011.05.012
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发表时间：
2011-09-01
影响因子：
6
通讯作者：
Kahari, Veli-Matti
中科院分区：
文献类型：
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作者：
Farshchian, Mehdi;Kivisaari, Atte;Kahari, Veli-Matti
由于累积的娱乐性暴露在阳光下，全球范围内角质形成细胞衍生的非黑色素瘤皮肤癌的发病率正在增加。目前，没有特定的分子标志物可用于评估癌前光化性角化病向侵袭性皮肤鳞状细胞癌（SCC）的进展。我们研究了丝氨酸蛋白酶抑制剂家族在皮肤鳞状细胞癌中的作用。皮肤 SCC 细胞系 (n = 8) 的表达谱显示，与正常表皮角质形成细胞 (n = 5) 相比，SerpinA1 上调。定量 RT-PCR 分析表明，与正常角质形成细胞相比，皮肤 SCC 细胞系 (n = 8) 中 SerpinA1 mRNA 的平均水平显着上调。 SCC 细胞产生的 SerpinA1 依赖于 p38 丝裂原激活蛋白激酶活性，并受表皮生长因子、肿瘤坏死因子-a、干扰素-γ 和 IL-1 β 上调。对 148 个人体组织样本进行的组织阵列免疫染色显示，在 36 个光化性角化病样本中的 19 个样本、29 个鲍文氏病样本中的 22 个样本、71 个散发性鳞状细胞癌中的 67 个样本以及所有 12 个隐性营养不良性大疱性表皮松解症相关鳞状细胞癌中，SerpinA1 的肿瘤细胞相关表达。此外，在所有研究的化学诱导小鼠皮肤 SCC 中均检测到肿瘤细胞相关的 SerpinA1 染色 (n = 17)。与对照组织 (n = 14) 相比，化学诱导的小鼠皮肤 SCC (n = 14) 中也通过定量 RT-PCR 检测到了 SerpinA1 mRNA 的过表达。这些数据将 SerpinA1 确定为皮肤 SCC 进展的新型肿瘤细胞相关生物标志物。 （Am J Pathol 2011，179：1110-1119；DOI：10.1016/j.ajpath.2011.05.012）
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 up-regulated by epidermal growth factor, tumor necrosis factor-a, interferon-gamma, and IL-1 beta. 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. (Am J Pathol 2011, 179:1110-1119; DOI: 10.1016/j.ajpath.2011.05.012)