Mucin 5AC-Mediated CD44/ITGB1 Clustering Mobilizes Adipose-Derived Mesenchymal Stem Cells to Modulate Pancreatic Cancer Stromal Heterogeneity.

ABSTRACT:

Background & aims

Secreted mucin 5AC (MUC5AC) promotes pancreatic cancer (PC) progression and chemoresistance, suggesting its clinical association with poor prognosis. RNA sequencing analysis from the autochthonous pancreatic tumors showed a significant stromal alteration on genetic ablation of Muc5ac. Previously, depletion or targeting the stromal fibroblasts showed an ambiguous effect on PC pathogenesis. Hence, identifying the molecular players and mechanisms driving fibroblast heterogeneity is critical for improved clinical outcomes.

Methods

Autochthonous murine models of PC (Kras^G12D, Pdx1-Cre [KC] and Kras^G12D, Pdx1-Cre, Muc5ac^-/- [KCM]) and co-implanted allografts of murine PC cell lines (Muc5ac wild-type and CRISPR/Cas knockout) with a

SUBMITTER: Ganguly K 

PROVIDER: S-EPMC9117481 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature