Abstract：
Podoplanin (PDPN) is widely used as a marker of lymphatic endothelial cells. PDPN is also involved in tumor progression, and upregulated PDPN expression is often found in various cancers. In this study, we first immunohistochemically examined PDPN expression in 87 cases of Bowen disease. Positive expression was detected in 64.4% of Bowen disease specimens, and the positive cells were exclusively located in the basal layer and corresponded to palisaded basal cells (PBCs). PBCs have been considered to be residual normal keratinocytes so far, but PDPN expression in cancers is generally associated with poor clinical outcomes. We also examined PDPN expression in 27 cases of Bowen carcinoma. Diffuse and strong PDPN expression was detected in 22.2% of Bowen carcinoma specimens, and another 22.2% showed PDPN expression at the leading edges of tumor nests. These results prompted us to determine whether PDPN-positive cells are more tumorigenic than PDPN-negative cells. We cultured Bowen disease cells using a three-dimensional (3D) cell culture system and examined PDPN expression. In the cultured Bowen disease tissue, PDPN expression was again detected in the basal layer. Then, we isolated 1.2 × 105 PDPN-positive and -negative cells from the 3D organotypic culture of Bowen disease by fluorescence-activated cell sorting analysis and compared their tumorigenicity using 3D culture. The PDPN-positive tumor cells were able to regenerate Bowen disease tissue, but the PDPN-negative tumor cells were not. In addition, the regenerated Bowen disease tissue derived from the PDPN-positive cells exhibited PDPN expression in its basal layer, as the parental Bowen disease tissue did. These results indicate that PDPN-positive cells include tumor cells with cancer stem cell properties. Although the precise mechanism through which PDPN expression is involved in the pathogenesis of Bowen disease needs to be determined, PDPN may be a novel druggable target for Bowen disease.
摘要：
Podoplanin（PDPN）被广泛用作淋巴内皮细胞的标志物。PDPN也参与肿瘤进展，和上调的PDPN表达通常在各种癌症中发现。在这项研究中,我们首先用免疫组织化学方法检测了87例Bowen病中PDPN的表达。在Bowen病标本中检测到64.4%的阳性表达，阳性细胞仅位于基底层，对应于栅栏状基底细胞（PBC）。到目前为止，PBC被认为是残留的正常角质形成细胞，但PDPN在癌症中的表达通常与不良临床结局相关。我们还检测了27例Bowen癌中PDPN的表达。在22.2%的Bowen癌标本中检测到弥漫性和强PDPN表达，另有22.2%的人在肿瘤巢的前缘显示PDPN表达。这些结果促使我们确定PDPN阳性细胞是否比PDPN阴性细胞更具致瘤性。我们使用三维（3D）细胞培养系统培养了Bowen病细胞，并检查了PDPN表达。在培养的鲍恩病组织中，在基底层中再次检测到PDPN表达。然后，我们通过荧光激活细胞分选分析从Bowen病的3D器官型培养物中分离出1.2×105个PDPN阳性和阴性细胞，并使用3D培养比较了它们的致瘤性。PDPN阳性肿瘤细胞能够再生Bowen病组织,但PDPN阴性肿瘤细胞没有。此外,来自PDPN阳性细胞的再生Bowen病组织在其基底层表现出PDPN表达，就像父母的鲍恩病组织一样。这些结果表明PDPN阳性细胞包括具有癌症干细胞特性的肿瘤细胞。尽管PDPN表达参与Bowen病发病的确切机制尚待确定,PDPN可能是Bowen病的新的药物靶标。
