Low molecular weight hyaluronan induces migration of human choriocarcinoma JEG-3 cells mediated by RHAMM as well as by PI3K and MAPK pathways

Abstract

Hyaluronan (HA) is the major glycosaminoglycan present in the extracellular matrix. It is produced by some tumours and promotes proliferation, differentiation and migration among others cellular processes. Gestational trophoblastic disease (GTD) is composed by non-tumour entities, such as hydatidiform mole (HM), which is the most common type of GTD and also malignant entities such as choriocarcinoma (CC) and placental site trophoblastic tumour (PSTT), being CC the most aggressive tumour. Although there is a growing understanding of GTD biology, the role of HA in the pathogenesis of this group of diseases remains largely unknown. The aim of this work was to study the role of HA in the pathogenesis of GTD by defining the expression pattern of HA and its receptors CD44 and RHAMM, as well as to determine if HA can modulate proliferation, differentiation and migration of CC cells. Receptors and signalling pathways involved were also analyzed. We demonstrated that HA and RHAMM are differently expressed among GTD entities and even among trophoblast subtypes. We also showed that HA is able to enhance the expression of extravillous trophoblast markers and also to induce migration of JEG-3 cells, the latter mediated by RHAMM as well as PI3K and MAPK pathways. These findings indicate a novel regulatory mechanism for CC cell biology and also contribute to the understanding of GTD pathophysiology.

Glioma infiltration and extracellular matrix: key players and modulators

“…Similarly, CD44, RHAMM can undergo alternative splicing, particularly in cancer cells (Assmann, Marshall, Fieber, Hofmann, & Hart, ; Kong et al, ; Villegas‐Ruíz et al, ). Interactions of HA with RHAMM can trigger a number of cellular signaling pathways involving protein kinase C (PKC), focal adhesion kinases (FAK), MAP kinases, Ras GTPases, phosphatidylinositol kinase (PI3K), tyrosine kinases and cytoskeletal components (Gouëffic et al, ; Hall et al, ; Mascaro et al, ; Twarock, Tammi, Savani, & Fischer, ; Wang et al, ). CD44 and RHAMM are independent receptors (for instance, in a prostate‐cancer cell series, RHAMM, but not CD44, is present; Gurski et al, ).…”

Efficacy of Low Molecular Heparin on Preeclampsia by Inhibiting Apoptosis of Trophoblasts via the p38MAPK Signaling Pathway

“…Interestingly, the p38MAPK signaling pathway has effects similar to those of low molecular heparin [ 9 , 10 ], which suggests that low molecular heparin may affect preeclampsia like the p38MAPK signaling pathway. It has been reported that activating the MAPK signaling pathway is an action mechanism of low molecular heparin in promoting the migration of trophoblasts [ 11 ].…”

Bioinformatics Analysis of Choriocarcinoma-Related MicroRNA-Transcription Factor-Target Gene Regulatory Networks and Validation of Key miRNAs

“… 31 CD44, the receptor of hyaluronic acid, was demonstrated to be highly expressed in choriocarcinoma cells, facilitate tumour cell adhesion to the extracellular matrix and basement membrane and to provide sites for tumour invasion. 32 Lan et al revealed that CDH1 expression was significantly increased in JEG-3 and JAR cells compared with HTR-8/SVneo cells, and DNA methylation of the CDH1 promoter contributed to choriocarcinoma cell motility and invasion. 33 TGF-β2 was dramatically downregulated in choriocarcinoma cell lines (JEG-3 and JAR) compared with a normal trophoblast cell line (HTR-8/SVneo).…”