The data so far suggest that in vivo within the aggressiveness niche, secretion of IL-1β by IRISOE cells is exacerbated by hypoxia, and acts in paracrine fashion to elevate expression of IL-1R on the surface of naïve MSCs, recruits them to the vicinity of tumor cells in the niche, activates AKT, ERK, and NF-κB signaling in them, leading to production/secretion of CXCL1 from MSCs, which also in paracrine fashion activates IRISOE tumor cells (see model in Figure 2I). Here, AKT1 is linked to neoplasm.