Skip to main content
. Author manuscript; available in PMC: 2019 Apr 1.
Published in final edited form as: Biochem Pharmacol. 2018 Feb 13;150:170–180. doi: 10.1016/j.bcp.2018.02.011

Figure 3. Mechanism of FFA4-mediated chemoresistance to the platinum-induced PUFA 16:4(n-3).

Figure 3

Mesenchymal stem cells (MSC) localized to the tumor microenvironment produce 16:4(n-3) PUFA in response to platinum-based chemotherapeutics such as cisplatin via an intracellular signaling mechanism that is dependent on Ca+2, PLA2, thromboxane synthase (TXAS), and cyclooxygenase-1 (COX1) (86). 16:4(n-3) that is released by MSC agonizes FFA4 on splenic macrophages (F4/80+/CD11blow in mice, presumably CD163+ in humans) to activate cytosolic PLA2 via an unresolved pathway that is likely Gαq/11/Ca+2-mediated. FFA4-induced activation of cPLA2 forms the lysophosphatidylcholine LPC(24:1), which directly alters the ability of platinum-based chemotherapeutics to mediate DNA damage responses in cancer cells, leading to chemoresistance to the agents (88–89).