癌症研究
肿瘤微环境
间质细胞
下调和上调
转录组
腹膜腔
腺癌
河马信号通路
基因表达谱
生物
细胞生长
医学
病理
癌症
基因
基因表达
内科学
肿瘤细胞
遗传学
生物化学
解剖
作者
Vinay K. Pattalachinti,Ichiaki Ito,Saikat Chowdhury,Abdelrahman Yousef,Yue Gu,Betul Beyza Gunes,Emma R. Salle,Melissa W. Taggart,Keith F. Fournier,Natalie W. Fowlkes,John Paul Shen
标识
DOI:10.1158/1541-7786.mcr-23-0749
摘要
Appendiceal adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDX) to study the effect of the peritoneal microenvironment on AA. AA tumors implanted in the peritoneal microenvironment tended to grow faster and displayed greater nuclear expression of Ki-67 relative to the same tumors implanted in the flank. Comparing the tumor-specific transcriptome (excluding stromal transcription), the peritoneal microenvironment relatively upregulated genes related to proliferation, including MKI67 and EXO1. Peritoneal tumors were also enriched for proliferative gene sets, including E2F and Myc Targets. Proteomic studies found a 2.5-fold increased ratio of active-to-inactive phosphoforms of the YAP oncoprotein in peritoneal tumors, indicating downregulation of Hippo signaling.The peritoneal microenvironment promotes growth of appendiceal tumors and expression of proliferative pathways in PDXs.
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