TGFβ1 and Oncostatin M promotes the organization of two distinct stromal niches controlling different EMT states

Bioinformatic prediction of the ligand-receptor pairs that regulate the communication between immune and tumor cells identified oncostatin M (OSM) as secreted by neutrophils and macrophages and interacted with hybrid EMT state whereas TGFβ1 expressed by macrophages and other stromal cells communicated with late EMT states. Functional validation showed that unlike TGFβ1, which only upregulated EMT program and promotes late EMT state, OSM partially activates EMT transcription factors while sustaining the epithelial program, promoting hybrid EMT states.

In addition, both OSM and TGFβ1 function in a feed-forward manner by creating distinct inflammatory niches to maintain specific EMT states. Altogether, our results reveal that different niches are associated with different EMT states, and different signaling pathways sustain the creation of their own niche by attracting different immune cells.