TNF and neoplasm: For instance, in Lewis lung carcinoma, the tumor-derived proteoglycan versican can stimulate host macrophages to assume an M1 phenotype, culminating in the secretion of TNF-α and the creation of an inflammatory microenvironment.184 Furthermore, Chang et al. showed that IL-6 secreted by advanced-stage invasive breast cancer cells can activate STAT3 via JAK signaling, affecting both the tumor cells and the surrounding stromal cells.