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Transcriptional Expression of Genes Involved in Cell Invasion and Migration by Normal and Tumoral Trophoblast Cells

Laboratoire d’Immunologie des Tumeurs ESA 8067 CNRS (J.L.J., D.B.), Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes-Paris 5, Paris, Equipe cytokines et régulation marterno-foetale, U131 INSERM (J.M.E., G.C.), Service de Biologie et Génétique de la Reproduction (G.T.), Service de Gynécologie Obstétrique (B.S., R.F.), Hôpital Antoine Béclère, Clamart, France; University of Antioquia (J.M.E.), Medellin, Columbia; and Service de Biologie Oncologique (I.M., N.M., P.S., D.B.) and Service d’Anatomie Pathologique (J.C.S., J.F.C.), Institut Gustave Roussy, Villejuif, France

Address correspondence to: Dominique Bellet, M.D., Service de Biologie Oncologique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.

Abstract

Once initiated, invasion of trophoblast cells must be tightly regulated, particularly in early pregnancy. The mechanisms necessary for the invasion and migration of trophoblast cells are thought to be related to those involved in the invasive and metastatic properties of cancer cells. Quantitative PCR was used to measure, in trophoblast cells, the transcriptional expression profiles of four genes, INSL4, BRMS1, KiSS-1 and KiSS-1R, reported to be implicated in tumor invasion and metastasis. Laser capture microdissection and purification of trophoblast cells demonstrate that, as already known for INSL4, BRMS1, KiSS-1 and KiSS-1R are expressed by the trophoblast subset of placental tissues. Expression profiles of these genes studied in early placentas (7–9 weeks, n=55) and term placentas (n=11) showed that expression levels of BRMS1 are higher in term than in early placentas, while expression levels of KiSS-1R are higher in early than in term placentas. Low levels of expression of BRMS1 were observed in normal pregnancies, in molar pregnancies and in choriocarcinoma cell lines BeWo, JAR and JEG3 while, in striking contrast, the expression levels of INSL4, KiSS-1 and Kiss-1R were increased in both early placentas and molar pregnancies and were reduced in choriocarcinoma cells. These transcriptional expression profiles are in favor of a predominant role of INSL4, KiSS-1 and KiSS-1R in the control of the invasive and migratory properties of trophoblast cells.

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