Pancreatic ductal adenocarcinoma (PDAC) is characterized by extracellular matrix-rich stromal involvement, but it is not
clear how ECM properties that affect invasiveness and chemotherapy response influence efficacy of photodynamic
therapy (PDT). To disentangle the mechanical and biochemical effects of ECM composition, we measured the effects of
various combinations of ECM proteins on growth behavior, invasive potential, and therapeutic response of multicellular
3D pancreatic tumor models. These spheroids were grown in attachment-free conditions before embedding in
combinations of rheologically characterized collagen 1 and Matrigel combinations and treated with oxaliplatin
chemotherapy and PDT. We find that cells invading from collagen-embedded tumor spheroids, the least rigid ECM
substrate described here, displayed better response to PDT than to oxaliplatin chemotherapy. Overall, our results support
that ECM-mediated invading PDAC populations remain responsive to PDT in conditions that induce chemoresistance.
|