Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid

Ayako Uchiyama, Mutsuko Mukai, Yuko Fujiwara, Susumu Kobayashi, Nobuyuki Kawai, Hiromu Murofushi, Masahiro Inoue, Shigenori Enoki, Yuichiro Tanaka, Tamotsu Niki, Tetsuyuki Kobayashi, Gabor Tigyi, Kimiko Murakami-Murofushi

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1771
Issue number1
DOIs
StatePublished - Jan 1 2007

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Transcellular Cell Migration
Phosphatidic Acids
Neoplasm Metastasis
Phosphates
Neoplasms
Lysophosphatidic Acid Receptors
Experimental Melanomas
Helper-Inducer T-Lymphocytes
Ether
Glycerol
Fatty Acids
lysophosphatidic acid
Oxygen
Lung

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid. / Uchiyama, Ayako; Mukai, Mutsuko; Fujiwara, Yuko; Kobayashi, Susumu; Kawai, Nobuyuki; Murofushi, Hiromu; Inoue, Masahiro; Enoki, Shigenori; Tanaka, Yuichiro; Niki, Tamotsu; Kobayashi, Tetsuyuki; Tigyi, Gabor; Murakami-Murofushi, Kimiko.

In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, Vol. 1771, No. 1, 01.01.2007, p. 103-112.

Research output: Contribution to journalArticle

Uchiyama, A, Mukai, M, Fujiwara, Y, Kobayashi, S, Kawai, N, Murofushi, H, Inoue, M, Enoki, S, Tanaka, Y, Niki, T, Kobayashi, T, Tigyi, G & Murakami-Murofushi, K 2007, 'Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid', Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, vol. 1771, no. 1, pp. 103-112. https://doi.org/10.1016/j.bbalip.2006.10.001
Uchiyama, Ayako ; Mukai, Mutsuko ; Fujiwara, Yuko ; Kobayashi, Susumu ; Kawai, Nobuyuki ; Murofushi, Hiromu ; Inoue, Masahiro ; Enoki, Shigenori ; Tanaka, Yuichiro ; Niki, Tamotsu ; Kobayashi, Tetsuyuki ; Tigyi, Gabor ; Murakami-Murofushi, Kimiko. / Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid. In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 2007 ; Vol. 1771, No. 1. pp. 103-112.
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