Fibroblast STAT3 Activation Drives Organ-Specific Premetastatic Niche Formation.

ABSTRACT: Pancreatic cancer is associated with a high rate of metastasis and poor prognosis. The formation of a premetastatic niche (PMN) facilitates cancer cell spread and contributes to cancer mortality. Using murine pancreatic cancer models based on expression of oncogenic KRAS in the pancreas epithelium, we discovered that remodeling of the lung microenvironment occurred in mice bearing pancreatic precursor lesions prior to cancer formation. This early-lesion PMN resembled the PMN in cancer-bearing mice, and both feature characteristics of overt metastasis, such as transcriptional reprogramming, activation of fibroblast STAT3 signaling, and infiltration of immunosuppressive arginase 1-positive macrophages. Both patients with pancreatic cancer and mouse models demonstrated elevated serum IL6. Ina

SUBMITTER: Lasse Opsahl EL 

PROVIDER: S-EPMC12757723 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature