Inhibition of tumor invasion and metastasis by a novel lysophosphatidic acid (cyclic LPA)

• Published in: International journal of cancer Vol. 81; no. 6; pp. 918 - 922
• Main Authors: Mukai, Mutsuko, Imamura, Fumio, Ayaki, Masako, Shinkai, Kiyoko, Iwasaki, Teruo, Murakami‐Murofushi, Kimiko, Murofushi, Hiromu, Kobayashi, Susumu, Yamamoto, Takashi, Nakamura, Hiroyuki, Akedo, Hitoshi
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 11.06.1999; Wiley-Liss
• Subjects: Actins - drug effects; Adenocarcinoma; Animals; Antineoplastic agents; Biological and medical sciences; Bucladesine - pharmacology; Cells, Cultured; Chemotherapy; Cyclic AMP - metabolism; Epithelial Cells - cytology; Epithelial Cells - drug effects; Fibrosarcoma; Humans; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Lysophospholipids - toxicity; Male; Medical sciences; Melanoma, Experimental - pathology; Melanoma, Experimental - prevention & control; Melanoma, Experimental - secondary; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness - prevention & control; Neoplasm Metastasis - prevention & control; Pancreatic Neoplasms; Pharmacology. Drug treatments; Rats; Structure-Activity Relationship; Tumor Cells, Cultured; Adenocarcinoma; Antineoplastic agent; Animal model; Spontaneous; Hepatic disease; Hepatocellular carcinoma; Fibrosarcoma; Metastasis; Bronchopulmonary; B16-Melanoma; Established cell line; Bronchus disease; Pancreas; Pancreatic disease; Human; Lung disease; Respiratory disease; Rodentia; Antimetastatic agent; Malignant tumor; In vitro; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Lysophosphatidic acid; Mouse; Animal; Digestive diseases
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990611)81:6<918::AID-IJC13>3.0.CO;2-E

Fetal calf serum (FCS) and 1‐oleoyl lysophosphatidic acid (LPA) were previously found to be potent inducers of invasion (transcellular migration) in an in vitro system. A novel LPA, composed of cyclic phosphate and cyclopropane‐containing hexadecanoic acid (PHYLPA), first isolated from myxoamoebae of Physarum polycephalum, and its synthetic derivatives (cLPA) were tested for their ability to inhibit tumor cell invasion and metastasis. Amoung these, Pal‐cLPA, which has a palmitoyl moiety, was most potent in inhibiting invasion, with 93.8% inhibition at the concentration of 25 μM. Invasion in vitro by mouse melanoma cells (B16), human pancreatic adenocarcinoma cells (PSN‐1), human lung cancer cells (OC‐10) and human fibrosarcoma cells (HT‐1080) was also inhibited by Pal‐cLPA. The stimulation of MM1 cells with LPA triggered F‐actin formation, which was impaired by the addition of Pal‐cLPA at invasion‐inhibitory concentration. Pal‐cLPA induced a rapid increase in adenosine 3′,5′‐cyclic monophosphate (cAMP) concentration in MM1 cells. The addition of dibutyryl cAMP significantly abrogated LPA‐induced invasion by MM1 cells and actin polymerization in the cells. The inhibition of MM1 cell invasion by Pal‐cLPA may be ascribed to an increased level of cAMP. Pal‐cLPA also suppressed invasion in vitro by MM1 cells induced by FCS dose dependently, without affecting proliferation. It also suppressed the pulmonary metastasis of B16 mouse melanoma cells injected into the tail vein of C57BL/6 mice. Thus, Pal‐cLPA is effective in inhibiting invasion and metastasis of a variety of tumor cells. Int. J. Cancer 81:918–922, 1999. © 1999 Wiley‐Liss, Inc.