Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases.

ABSTRACT: The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single disseminated cancer cells (DCCs) lacking expression of cytokeratin 19 (CK19) and major histocompatibility complex class I (MHCI). We created a mouse model to determine how these DCCs develop. Intraportal injection of immunogenic PDA cells into preimmunized mice seeded livers only with single, nonreplicating DCCs that were CK19^- and MHCI^- The DCCs exhibited an endoplasmic reticulum (ER) stress response but paradoxically lacked both inositol-requiring enzyme 1α activation and expression of the spliced form of transcription factor XBP1 (XBP1s). Inducible expression of XBP

SUBMITTER: Pommier A 

PROVIDER: S-EPMC6547380 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature