Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells
Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells
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DOI：
10.1046/j.1523-1747.2003.12379.x
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发表时间：
2003-08-01
影响因子：
6.5
通讯作者：
Burnstock, G
中科院分区：
文献类型：
--
作者：
Greig, AVH;Linge, C;Burnstock, G
我们研究了使用嘌呤能受体作为非黑色素瘤皮肤癌的新治疗方式。与 5'-三磷酸腺苷结合的嘌呤能受体在人皮肤角质形成细胞上表达。先前对大鼠和人表皮的研究表明嘌呤能受体在调节增殖、分化和细胞凋亡中的功能作用。对人基底细胞癌和鳞状细胞癌的冷冻切片进行 P2X(5) 、 P2X(7) 、 P2Y(1) 、 P2Y(2) 和 P2Y(4) 受体的免疫组织化学分析，同时对石蜡切片中肿瘤亚型的档案材料进行详细分析。使用人皮肤鳞状细胞癌细胞系 (A431) 进行功能研究，其中将嘌呤能受体亚型激动剂应用于细胞，并通过比色测定对细胞数量的变化进行量化。石蜡切片中的免疫染色与冷冻切片中的免疫染色基本相同，但可以看到更多的亚细胞组成细节。 P2X(5)和P2Y(2)受体在基底细胞癌和鳞状细胞癌中大量表达。 P2X(7) 受体在结节性基底细胞癌的坏死中心以及浅表多灶性和浸润性基底细胞癌以及鳞状细胞癌的凋亡细胞中表达。 P2Y(1)受体仅在肿瘤周围的基质中表达。 P2Y(4) 受体存在于基底细胞癌中，但未存在于鳞状细胞癌中。 P2X(5) 受体似乎与分化相关。 P2X(7) 受体激动剂苯甲酰苯甲酰基腺苷 5'-三磷酸和高浓度腺苷 5'-三磷酸 (1000-5000 muM) 导致 A431 细胞数量显着减少 (p
We investigated the use of purinergic receptors as a new treatment modality for nonmelanoma skin cancers. Purinergic receptors, which bind adenosine 5'-tri-phosphate, are expressed on human cutaneous keratinocytes. Previous work in rat and human epidermis suggested functional roles for purinergic receptors in the regulation of proliferation, differentiation, and apoptosis. Immunohistochemical analysis of frozen sections in human basal cell carcinomas and squamous cell carcinomas for P2X(5) , P2X(7) , P2Y(1) , P2Y(2) , and P2Y(4) receptors was performed, accompanied by detailed analysis of archive material of tumor subtypes in paraffin sections. Functional studies were performed using a human cutaneous squamous cell carcinoma cell line (A431), where purinergic receptor subtype agonists were applied to cells and changes in cell number were quantified via a colorimetric assay. Immunostaining in paraffin sections was essentially the same as that in frozen sections, although more detail of the subcellular composition was visible. P2X(5) and P2Y(2) receptors were heavily expressed in basal cell carcinomas and squamous cell carcinomas. P2X(7) receptors were expressed in the necrotic center of nodular basal cell carcinomas and in apoptotic cells in superficial multifocal and infiltrative basal cell carcinomas, and squamous cell carcinomas. P2Y(1) receptors were only expressed in the stroma surrounding tumors. P2Y(4) receptors were found in basal cell carcinomas but not in squamous cell carcinomas. P2X(5) receptors appear to be associated with differentiation. The P2X(7) receptor agonist benzoylbenzoyl-adenosine 5'-triphosphate and high concentrations of adenosine 5'-triphosphate (1000-5000 muM) caused a significant reduction in A431 cell number (p