Human Reproduction Update Advance Access originally published online on October 26, 2006
Human Reproduction Update 2007 13(2):121-141; doi:10.1093/humupd/dml048
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Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts
1 UMR 8149 CNRS, IFR 71, Université René Descartes, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Paris, France, 2 Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy and 3 Service de Médecine Nucléaire, Centre René Huguenin, Saint-Cloud, France
4 To whom correspondence should be addressed at: Laboratoire de Physiopathologie Hépatique et Laboratoire d’Immunologie, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, 4 Avenue de l’Observatoire, 75 006 Paris, France. E-mail: dominique.bellet{at}univ-paris5.fr
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Abstract |
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Trophoblast research over the past decades has underlined the striking similarities between the proliferative, migratory and invasive properties of placental cells and those of cancer cells. This review recapitulates the numerous key molecules, proto-oncogenes, growth factors, receptors, enzymes, hormones, peptides and tumour-associated antigens (TAAs) expressed by both trophoblastic and cancer cells in an attempt to evaluate the genes and proteins forming molecular circuits and regulating the similar behaviours of these cells. Among the autocrine and paracrine loops that might be involved in the strong proliferative capacity of trophoblastic and cancer cells, epidermal growth factor (EGF)/EGF receptor (EGFR), hepatocyte growth factor (HGF)/HGF receptor (HGFR) (Met) and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) loops may play a predominant role. Similar mechanisms of migration and invasion displayed by trophoblastic and malignant cells comprise alterations in the adhesion molecule phenotype, including the increased expression of 
1ß1 and vß3 integrin receptors, whereas another critical molecular event is the down-regulation of the cell adhesion molecule E-cadherin. Among proteases that may play an active role in the invasive capacities of these cells, accumulating evidence suggests that matrix metalloproteinase-9 (MMP-9) expression/activation is a prerequisite. Finally, an overview of molecular circuitries shared by trophoblast and cancer cells reveals that the activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT axis has recently emerged as a central feature of signalling pathways used by these cells to achieve their proliferative, migratory and invasive processes.
Key words: cell signalling / pregnancy / trophoblasts
Received on January 16, 2006; revised August 11, 2006; accepted on September 7, 2006
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