Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors

Abstract

Access to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Non-transformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known. By taking advantage of the endogenous fluorescence properties of reduced nicotinamide adenine dinucleotide cofactors and oxidized flavin adenine dinucleotide, we use optical imaging to assess the redox state of pancreatic cancer cells and PSCs and find that the redox state of cancer cells is more reduced while the redox state of PSCs is more oxidized. Direct interactions between PSCs and cancer cells promote a more oxidized state in cancer cells, suggesting that metabolic interactions between cancer cells and PSCs is a mechanism to overcome the redox limitations of cell proliferation in pancreatic cancer.

Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling

“…Although the influence of stromal cells such as tumor-associated fibroblasts and pancreatic stellate cells are well characterized in PDAC (46,(73)(74)(75)(76), the role of normal epithelial cells has not received as much scrutiny. We show that F. nucleatum infects nPECs using a Fap2-dependent mechanism, and this infection still results in the secretion of the same cytokines released by infected PDAC cells.…”

Fusobacterium nucleatum induces pancreatic cancer cell proliferation and migration by regulating host autocrine and paracrine signaling

“…While the influence of stromal cells such as tumor-associated fibroblasts and pancreatic stellate cells are well characterized in PDAC 40,[67][68][69][70] , the role of normal epithelial cells has not received as much scrutiny. Our results show that they too can regulate the fate of tumor cells.…”

Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from “first contact” interactions in the tumor microenvironment

“…Cells were cultured in FBS-containing media and shifted to medium containing exosome depleted-FBS prior to the experiment. A total of 10^8 cells were taken in each condition for the KPC cells alone or the PSC cells alone while for the co-culture condition, 9 times the number of PSCs were taken compared to the KPC cells mimicking conditions that are seen in vivo [16]. Cells were maintained in the exosome-depleted FBS containing media for 24 h and the supernatant was collected and concentrated using a 10KDa filter.…”