Details

Autor(en) / Beteiligte

• Patton, Mary C.
• Zubair, Haseeb
• Khan, Mohammad Aslam
• Singh, Seema
• Singh, Ajay P.

Titel

Hypoxia alters the release and size distribution of extracellular vesicles in pancreatic cancer cells to support their adaptive survival

Ist Teil von

• Journal of cellular biochemistry, 2020-01, Vol.121 (1), p.828-839

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2020

Quelle

Wiley-Blackwell Full Collection

Beschreibungen/Notizen

• Pancreatic tumors are highly desmoplastic and poorly‐vascularized, and therefore must develop adaptive mechanisms to sustain their survival under hypoxic condition. Extracellular vesicles (EV) play vital roles in pancreatic tumor pathobiology by facilitating intercellular communication. Here we studied the effect of hypoxia on the release of EVs and examined their role in adaptive survival of pancreatic cancer (PC) cells. Hypoxia promoted the release of EV in PC cell lines, MiaPaCa and AsPC1, wherein former exhibited a far greater induction. Moreover, a time‐dependent, measurable and significant increase was recorded for small EV (SEV) in both the cell lines with only minimal induction observed for medium (MEV) and large EVs (LEV). Similarly, noticeable changes in size distribution of SEV were also recorded with a shift toward smaller average size under extreme hypoxia. Thrombospondin (apoptotic bodies marker) was exclusively detected on LEVs, while Arf6 (microvesicles marker) was mostly present on MEV with some expression in LEV as well. However, CD9 and CD63 (exosome markers) were expressed in both SEV and MEVs with a decreased expression recorded under hypoxia. Among all subfractions, SEV was the most bioactive in promoting the survival of hypoxic PC cells and hypoxia‐inducible factor‐1α stabilization was involved in heightened EV release under hypoxia and for their potency to promote hypoxic cell survival. Altogether, our findings provide a novel mechanism for the adaptive hypoxic survival of PC cells and should serve as the basis for future investigations on broader functional implications of EV. Hypoxia‐induced changes in the release of extracellular vesicles (EV) by pancreatic tumor cells is an adaptive response mechanism. One of the functional significance is to promote their adaptive survival under hypoxia. Mechanistically, hypoxia‐inducible factor‐1α (HIF‐1α) plays an important role in altered release of EVs and their potency to promote cell survival.