2. Academic Validation
  3. Inhibition of transcellular tumor cell migration and metastasis by novel carba-derivatives of cyclic phosphatidic acid

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

  • Biochim Biophys Acta. 2007 Jan;1771(1):103-12. doi: 10.1016/j.bbalip.2006.10.001.
Ayako Uchiyama 1,  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
Affiliations

Affiliation

  • 1 Department of Biology, Faculty of Science, Ochanomizu University, 2-1-1 Ohtsuka, Tokyo 112-8610, Japan.
PMID: 17123862 DOI: 10.1016/j.bbalip.2006.10.001
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.

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