Genetic disruption or prolonged pharmacological inhibition of sonic hedgehog, a ligand that stimulates CAFs (Tian et al., 2009; Lee et al., 2014; Rhim et al., 2014), or depletion of αSMA-expressing cells (Özdemir et al., 2014), resulted in undifferentiated PDA tumors and decreased survival in mice
This sentence highlights a critical paradox in pancreatic cancer stroma research, where sonic hedgehog, secreated by cancer cells, is generally required for activation of CAFs in tumor stroma, but when its signaling was genetically or pharmacologically blocked or when αSMA-expressing myofibroblast-like CAFs were selectively depleted, tumors paradoxically became more aggressive and undifferentiated, with decreased mouse survival, indicating that tumor stroma is not necessarily always pro-tumorigenic. (source:https://doi.org/10.1016/j.ccr.2014.04.005, https://doi.org/10.1073/pnas.1411679111 )