研究动态
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伯温病基底层的Podoplanin阳性细胞包括具有癌干细胞特性的肿瘤细胞。

Podoplanin-positive cells located in the basal layer of Bowen disease include tumor cells with cancer stem cell properties.

发表日期:2023 Sep 02
作者: Kazutoshi Murao, Yoshiaki Kubo
来源: Cellular & Molecular Immunology

摘要:

Podoplanin(PDPN)被广泛用作淋巴内皮细胞的标记物。PDPN还参与肿瘤进展,并常见于多种癌症中上调表达。在本研究中,我们首次免疫组化检测了87例Bowen病患者的PDPN表达。阳性表达在Bowen病标本中检测到64.4%,阳性细胞仅位于基底层,与列阵成排基底细胞(PBCs)相对应。迄今为止,PBCs一直被认为是残余的正常角质细胞,但肿瘤中的PDPN表达通常与不良临床结局相关联。我们还检测了27例Bowen癌症中PDPN的表达。22.2%的Bowen癌标本中检测到弥漫和强烈的PDPN表达,另外22.2%显示PDPN表达位于肿瘤巢的前沿。这些结果促使我们确定PDPN阳性细胞是否比PDPN阴性细胞更具肿瘤形成能力。我们使用三维(3D)细胞培养系统培养Bowen病细胞,并检测PDPN表达。在培养的Bowen病组织中,PDPN表达再次检测到基底层。然后,我们通过流式细胞术从Bowen病的3D器官内培养中分离出1.2×105个PDPN阳性和阴性细胞,并使用3D培养比较它们的肿瘤形成能力。PDPN阳性肿瘤细胞能够再生Bowen病组织,但PDPN阴性肿瘤细胞不能。此外,由PDPN阳性细胞来源的再生Bowen病组织在其基底层表达PDPN,如原始Bowen病组织所示。这些结果表明PDPN阳性细胞包含具有肿瘤干细胞特性的肿瘤细胞。尽管尚需确定PDPN表达参与Bowen病发病机制的确切机制,但PDPN可能是Bowen病的新型药物靶点。© 2023日本皮肤科学会。
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.© 2023 Japanese Dermatological Association.