TY - JOUR
T1 - Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid
AU - Uchiyama, Ayako
AU - Mukai, Mutsuko
AU - Fujiwara, Yuko
AU - Kobayashi, Susumu
AU - Kawai, Nobuyuki
AU - Murofushi, Hiromu
AU - Inoue, Masahiro
AU - Enoki, Shigenori
AU - Tanaka, Yuichiro
AU - Niki, Tamotsu
AU - Kobayashi, Tetsuyuki
AU - Tigyi, Gabor
AU - Murakami-Murofushi, Kimiko
PY - 2007/1
Y1 - 2007/1
N2 - Cyclic phosphatidic acid (1-acyl-sn-glycerol-2,3-cyclic phosphate; cPA) is a naturally occurring analog of lysophosphatidic acid (LPA) with a variety of distinctly different biological activities from those of LPA. In contrast to LPA, a potent inducer of tumor cell invasion, palmitoyl-cPA inhibits FBS- and LPA-induced transcellular migration and metastasis. To prevent the conversion of cPA to LPA we synthesized cPA derivatives by stabilizing the cyclic phosphate ring; to prevent the cleavage of the fatty acid we generated alkyl ether analogs of cPA. Both sets of compounds were tested for inhibitory activity on transcellular tumor cell migration. Carba derivatives, in which the phosphate oxygen was replaced with a methylene group at either the sn-2 or the sn-3 position, showed much more potent inhibitory effects on MM1 tumor cell transcellular migration and the pulmonary metastasis of B16-F0 melanoma than the natural pal-cPA. The antimetastatic effect of carba-cPA was accompanied by the inhibition of RhoA activation and was not due to inhibition of the activation of LPA receptors.
AB - Cyclic phosphatidic acid (1-acyl-sn-glycerol-2,3-cyclic phosphate; cPA) is a naturally occurring analog of lysophosphatidic acid (LPA) with a variety of distinctly different biological activities from those of LPA. In contrast to LPA, a potent inducer of tumor cell invasion, palmitoyl-cPA inhibits FBS- and LPA-induced transcellular migration and metastasis. To prevent the conversion of cPA to LPA we synthesized cPA derivatives by stabilizing the cyclic phosphate ring; to prevent the cleavage of the fatty acid we generated alkyl ether analogs of cPA. Both sets of compounds were tested for inhibitory activity on transcellular tumor cell migration. Carba derivatives, in which the phosphate oxygen was replaced with a methylene group at either the sn-2 or the sn-3 position, showed much more potent inhibitory effects on MM1 tumor cell transcellular migration and the pulmonary metastasis of B16-F0 melanoma than the natural pal-cPA. The antimetastatic effect of carba-cPA was accompanied by the inhibition of RhoA activation and was not due to inhibition of the activation of LPA receptors.
KW - Cyclic phosphatidic acid
KW - Invasion
KW - Lysophosphatidic acid, LPA
KW - Metastasis
UR - http://www.scopus.com/inward/record.url?scp=33846066349&partnerID=8YFLogxK
U2 - 10.1016/j.bbalip.2006.10.001
DO - 10.1016/j.bbalip.2006.10.001
M3 - 記事
C2 - 17123862
AN - SCOPUS:33846066349
SN - 1388-1981
VL - 1771
SP - 103
EP - 112
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 1
ER -
