Hashikawa Keiko, Yasumoto Shinichiro, Nakashima Kazutaka, Arakawa Fumiko, Kiyasu Junichi, Kimura Yoshizo, Saruta Hiroshi, Nakama Takekuni, Yasuda Kaori, Tashiro Kosuke, Kuhara Satoru, Hashimoto Takashi, Ohshima Koichi
Department of Dermatology, Kurume University School of Medicine, Japan.
Department of Pathology, Kurume University School of Medicine, Japan.
Int J Oncol. 2014 Sep;45(3):1200-8. doi: 10.3892/ijo.2014.2524. Epub 2014 Jun 26.
The characteristic histopathological feature of mycosis fungoides (MF) and adult T-cell leukemia/lymphoma (ATLL) is epidermotropism. To identify the mechanism for epidermotropism of lymphoma cells, total RNAs were obtained from skin biopsies of epidermis and dermis of MF and ATLL patients by means of laser capture microdissection, and used for subsequent complementary DNA (cDNA) microarray experiments. This procedure has made it possible for us to observe and evaluate the regional environment of MF and ATLL. Hierarchical cluster analysis revealed that the cDNAs could be clearly differentiated into MF and ATLL. CCL27 was expressed in the dermis generated from keratinocytes, CCR4/CCR6/CCR7/CCR10/cutaneous lymphocyte-associated antigen (CLA) lymphoma cells in the dermis, and CCL21 in the extracellular matrix (stroma). Lymphotoxin (LT) β and CCL21 expression was significantly higher and that of CCR10 relatively for MF, while CCR4 and CLA expression was relatively higher for ATLL. In the epithelium, keratinocytes expressed CCL20/CCL27, and lymphoma cells CCR4/CCR6/CCR10, while CCR4, CCR6, CCL20 and CCL27 expression was relatively higher for ATLL than MF. The dermis of MF, but not that of ATLL, showed correlation between CCR7 and CCL21. These findings support the suggestion that chemokines and chemokine receptors are involved in the pathogenesis of MF and ATLL, indicate that cutaneous homing seems to be different for MF and ATLL, and point to the possibility that cutaneous T-cell lymphomas originate in regulatory T cells, especially in the case of ATLL.
蕈样肉芽肿（MF）和成人T细胞白血病/淋巴瘤（ATLL）的特征性组织病理学特征是亲表皮性。为了确定淋巴瘤细胞亲表皮性的机制，通过激光捕获显微切割从MF和ATLL患者的表皮和真皮皮肤活检组织中获取总RNA，并用于后续的互补DNA（cDNA）微阵列实验。这一过程使我们能够观察和评估MF和ATLL的局部环境。层次聚类分析显示，cDNA可明显分为MF和ATLL两类。CCL27在角质形成细胞产生的真皮中表达；CCR4/CCR6/CCR7/CCR10/皮肤淋巴细胞相关抗原（CLA）在真皮中的淋巴瘤细胞中表达；CCL21在细胞外基质（基质）中表达。淋巴毒素（LT）β和CCL21在MF中的表达显著较高，CCR10的表达相对较高；而CCR4和CLA在ATLL中的表达相对较高。在上皮中，角质形成细胞表达CCL20/CCL27，淋巴瘤细胞表达CCR4/CCR6/CCR10，而ATLL中CCR4、CCR6、CCL20和CCL27的表达比MF相对更高。MF的真皮，而非ATLL的真皮，显示CCR7与CCL21之间存在相关性。这些发现支持趋化因子和趋化因子受体参与MF和ATLL发病机制的观点，表明MF和ATLL的皮肤归巢似乎不同，并指出皮肤T细胞淋巴瘤可能起源于调节性T细胞，尤其是在ATLL的情况下。
