Lymphocyte Antigen 6 Family Member D (LY6D) Affects Stem Cell Phenotype and Progression of Pancreatic Adenocarcinoma.

IF 1.6 4区医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17300

Shumpei Okimura, Naohiro Nishida, Hidekazu Takahashi, Yuhki Yokoyama, Hiroyuki Yamamoto, Atsushi Hamabe, Takayuki Ogino, Norikatsu Miyoshi, Hidenori Takahashi, Mamoru Uemura, Shogo Kobayashi, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hirofumi Yamamoto

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Abstract

Background/aim: The membrane-bound protein lymphocyte antigen 6 family member D (LY6D), a marker of early B cell lineage is reportedly expressed in several human malignancies and has been implicated in cancer stemness. However, its expression and role in cancer stemness remain largely unexplored in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to clarify the role of LY6D in PDAC.

Materials and methods: We conducted functional analysis of LY6D to evaluate its impact on the malignant features of PDAC cells in vitro. Using our in-house developed stem cell separation technique, which isolates cells with low proteasome activity and CD44 v9 cell surface marker for cancer stem cells, we performed sphere formation and chemosensitivity tests and tumor formation assay in mice, through knockdown of LY6D expression. Immuno-histopathological analysis was also conducted to reveal the clinical significance of LY6D in PDAC.

Results: In vitro functional assays demonstrated that LY6D was critically involved in promoting the cancer malignant phenotype, including increased invasive ability, drug resistance, migration capacity, and cancer stemness. Immunohistopathological analysis revealed that high LY6D expression levels were associated with high recurrence rates and poorer prognosis in PDAC.

Conclusion: Our study showed that LY6D is a novel prognostic indicator and plays a key role in regulation of cancer stemness in PDAC.

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淋巴细胞抗原 6 家族成员 D (LY6D) 影响干细胞表型和胰腺癌的进展

背景/目的：据报道，膜结合蛋白淋巴细胞抗原6家族成员D（LY6D）是早期B细胞系的标志物，在多种人类恶性肿瘤中均有表达，并与癌症干性有关。然而，它在胰腺导管腺癌（PDAC）中的表达及其在癌症干性中的作用在很大程度上仍未得到探讨。本研究旨在阐明 LY6D 在 PDAC 中的作用：我们对 LY6D 进行了功能分析，以评估其对体外 PDAC 细胞恶性特征的影响。利用我们自主开发的干细胞分离技术（该技术可分离出蛋白酶体活性低的细胞和癌症干细胞的CD44 v9细胞表面标志物），我们通过敲除LY6D的表达，在小鼠体内进行了球形成和化疗敏感性试验以及肿瘤形成试验。我们还进行了免疫组织病理学分析，以揭示 LY6D 在 PDAC 中的临床意义：结果：体外功能测试表明，LY6D在促进癌症恶性表型方面起着关键作用，包括增强侵袭能力、耐药性、迁移能力和癌症干性。免疫组织病理学分析表明，LY6D的高表达水平与PDAC的高复发率和较差的预后有关：我们的研究表明，LY6D是一种新的预后指标，在PDAC的癌症干性调控中发挥着关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.