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Lysophosphatidic acid (LPA) acts via G protein coupled receptors (GPCRs) to regulate critical cellularfunctions and pathophysiological levels of LPA or its receptors are linked to cancer initiation, progression andmetastasis. LPA is biosynthesized by the lysophospholipase D activity of autotaxin (ATX/lysoPLD), a known factor fortumorigenesis. By attenuating both LPA signaling and LPA production, we expected to observe synergistic anti-cancertherapeutic effects. In vitro, treatment of human colon cancer cells (HCT 116) with BrP-LPA, a potent dual action ATXinhibitor and pan-LPA GPCR antagonist, significantly reduced cell proliferation, migration and invasion. Next, a tissueengineeredxenograft model to mimic hepatic metastasis of colon cancer was used to evaluate BrP-LPA efficacy in vivo.HCT 116 cells were suspended in Extracel™, a synthetic extracellular matrix (sECM), and injected directly into the liversof nude mice (n = 8). After 1 week, BrP-LPA in saline buffer was administered for two weeks by intraperitoneal injection(10 mg/kg) twice per week. Controls were injected with saline buffer only. The BrP-LPA treated group showed reducedliver tumor weight (p < 0.05) and reduced tumor volume (p < 0.05) relative to controls. This study is the firstdemonstration of the effects of a dual action ATX inhibitor/LPA antagonist on colon cancer cells, and the first example ofa tissue-engineered hepatic colon cancer “metastases” as a platform for anti-cancer drug evaluation. The results suggestthat attenuation of signaling through the LPA pathway offers a promising therapeutic target for reducing colon cancergrowth and metastasis.

Tissue-Engineered “Metastases”: Treatment of Hepatic Colon Tumors with a Dual Action Autotaxin Inhibitor-Lysophosphatidic Acid Receptor Antagonist