Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts.
Mol Cancer Res
; 22(4): 329-336, 2024 04 02.
Article
en En
| MEDLINE
| ID: mdl-38226984
ABSTRACT
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. IMPLICATIONS The peritoneal microenvironment promotes growth of appendiceal tumors and expression of proliferative pathways in PDXs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias del Apéndice
/
Neoplasias Peritoneales
/
Adenocarcinoma
Límite:
Humans
Idioma:
En
Revista:
Mol Cancer Res
/
Mol. cancer res
/
Molecular cancer research
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2024
Tipo del documento:
Article