CCL2 and cancer: We later noted that TAMs surrounding necrotic foci in 4T1 tumors were associated with high levels of Ccl2 mRNA by ISH, and supernatants of necrotic 4T1 cells upregulated CCL2 production by TG-induced macrophages in vitro, suggesting that molecules released from necrotic cancer cells are also involved in the production of CCL2 and likely other cancer-promoting factors present in TMEs [164].