透明带 3 (ZP3) 表达通常出现在卵母细胞的 ZP 层中，最近在卵巢癌和前列腺癌中得到证实。 ZP3 卵巢癌免疫疗法在转基因小鼠中取得成功，表明它可以作为一个有吸引力的治疗靶点。 ZP3 在癌症生长和进展中的生物学作用仍不清楚。我们发现约 88% 的分析腺癌、鳞状细胞癌和小细胞肺癌表达 ZP3。在表达 ZP3 的肺腺癌细胞系中敲除 ZP3，可显着降低体外细胞活力、增殖和迁移率。将透明带 3 敲除 (ZP3-KO) 细胞肿瘤体内接种到免疫缺陷非肥胖糖尿病、严重联合免疫缺陷小鼠体内，显示出对肿瘤生长的显着抑制和恶性表型的减轻。 RNA 测序揭示了 ZP3-KO 细胞中细胞迁移/粘附信号通路的失调。 ZP3 在肺癌中的这种新颖的功能相关性强调了 ZP3 作为癌症免疫治疗靶点和潜在癌症生物标志物的适用性。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Zona pellucida 3 (ZP3) expression is classically found in the ZP-layer of the oocytes, lately shown in ovarian and prostate cancer. A successful ZP3 ovarian cancer immunotherapy in transgenic mice suggested its use as an attractive therapeutic target. The biological role of ZP3 in cancer growth and progression is still unknown. We found that ~88% of the analyzed adenocarcinoma, squamous and small cell lung carcinomas to express ZP3. Knockout of ZP3 in a ZP3-expressing lung adenocarcinoma cell line, significantly decreased cell viability, proliferation, and migration rates in vitro. Zona pellucida 3 knock out (ZP3-KO) cell tumors inoculated in vivo in immunodeficient non-obese diabetic, severe combined immunodeficient mice showed significant inhibition of tumor growth and mitigation of the malignant phenotype. RNA sequencing revealed the deregulation of cell migration/adhesion signaling pathways in ZP3-KO cells. This novel functional relevance of ZP3 in lung cancer emphasized the suitability of ZP3 as a target in cancer immunotherapy and as a potential cancer biomarker.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.