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Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo

Year: 2012
Type: article
Abstract: Pancreatic cancer is highly metastatic and has a poor prognosis. However, there is no established treatment for pancreatic cancer. Lysophosphatidic acid (LPA) has been shown to be present in effluents of cancers and involved in migration and proliferation in a variety of cancer cells, including pancreatic cancer cells, in vitro. In the current study, we examined whether an orally active LPA antagonist is effective for pancreatic cancer tumorigenesis and metastasis in vivo. Oral administration of Ki16198, which is effective for LPA(1) and LPA(3), into YAPC-PD pancreatic cancer cell-inoculated nude mice significantly inhibited tumor weight and remarkably attenuated invasion and metastasis to lung, liver, and brain, in association with inhibition of matrix metalloproteinase (MMP) accumulation in ascites in vivo. Ki16198 inhibited LPA-induced migration and invasion in several pancreatic cancer cells in vitro, which was associated with the inhibition of LPA-induced MMP production. In conclusion, Ki16198 is a promising orally active LPA antagonist for inhibiting the invasion and metastasis of pancreatic cancer cells. The inhibitory effects of the antagonist on invasion and metastasis in vivo may be partially explained by the inhibition of motility activity and MMP production in cancer cells.
DOI: 10.1111/j.1349-7006.2012.02246.x
Authors: Mayumi Komachi, Koichi Sato, Masayuki Tobo, Chihiro Mogi, Takayuki Yamada, Hideo Ohta, Hideaki Tomura, Takao Kimura, Dong‐Soon Im, Keisuke Yanagida, Satoshi Ishii, Izumi Takeyoshi, Fumikazu Okajima
Institutions: Gunma University, Institute for Molecular and Cellular Regulation, Gunma University, Kyowa Kirin (Japan), Pusan National University, The University of Tokyo, Akita University
Language: English
Open Access status: green
Awards: Role of host proton-sensing receptors in tumorigenesis: analysis with receptor-deficient mice, Involvement of ABCA1 transporter in the regulation of anti-atherogenic sphingosine-1-phosphate content in plasma and high-density lipoprotein, Role of proton-sensing G protein-coupled receptors on microglial activation and neuronal cell survival in a ischemic situation., The role of proton-sensing G-protein coupled receptors(GPCRs) in the regulation of inflammatory cytokine production during endoscopic surgery, Targeting bioactive lipid receptors for drug development, Role of the G-protein-coupled receptors that sense an extracellular pH in a bone and a joint function, The role of proton-sensing G protein coupled receptor in bone remodeling, Novel roles of lysolipid receptors : proton sensing and its biological function, G8886373233
OpenAlex ID: W2064686830
FWCI: 1.89
Cites: 34
Cited by: 55
Related to: 10