ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells
Menée in vitro et in vivo, cette étude met en évidence le rôle joué par le facteur stimulé par l'interféron ISG15 dans le renforcement des propriétés invasives de cellules souches cancéreuses d'un adénocarcinome canalaire du pancréas
Cancer stem cells (CSC) are thought to play a major role in the development and metastatic progression of pancreatic ductal adenocarcinoma (PDAC), one of the deadliest solid tumors. Likewise, the tumor microenvironment contributes critical support in this setting, including from tumor stromal cells and tumor-associated macrophages (TAM) that contribute structural and paracrine-mediated supports, respectively. Here we show that TAM secrete the interferon-stimulated factor ISG15 which enhances CSC phenotypes in PDAC in vitro and in vivo. ISG15 was preferentially and highly expressed by TAM present in primary PDAC tumors resected from patients. ISG15 was secreted by macrophages in response to secretion of interferon-beta; by CSC, thereby reinforcing CSC self-renewal, invasive capacity and tumorigenic potential. Overall, our work demonstrates that ISG15 is a previously unrecognized support factor for CSC in the PDAC microenvironment with a key role in pathogenesis and progression.