Leptin promotes human endometriotic cell migration and invasion by up-regulating MMP-2 through the JAK2/STAT3 signaling pathway

Abstract

Despite evidence that leptin may play a role in the pathogenesis of endometriosis, the specific function of leptin in the migration and invasion of endometriotic cells is not well characterized. In this study, we investigated the effect of leptin on the migration, invasion and matrix metalloproteinase (MMP) expression levels of human endometriotic cells. We found that leptin stimulated the migration and invasion of endometriotic cells (11Z, 12Z and 22B) in a dose-dependent manner. Leptin receptor (ObR) siRNA significantly inhibited the migration and invasion induced by leptin in 11Z and 12Z cells. Leptin-induced migration and invasion were significantly attenuated by pretreatment with SB-3CT, a specific gelatinase (MMP-2 and MMP-9) inhibitor. In addition, leptin-induced increases in the mRNA and protein expression and enzyme activity of MMP-2 in 11Z and 12Z cells. Selectively inhibiting MMP-2 using siRNA and an inhibitor (GM6003), impaired the ability of leptin to stimulate the migration and invasion of endometriotic cells, suggesting that MMP-2 plays an essential role in leptin-induced migration and invasion. Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) inhibitor (AG490) significantly inhibited the migration, invasion and MMP-2 expression induced by leptin in endometriotic cells. Furthermore, the Extracellular signal-Regulated Kinase inhibitor PD98059 neutralized the migration and invasion promoting effects of leptin. Taken together, these results suggest that leptin may contribute to the migration and invasion abilities of endometriotic cells via the up-regulation of MMP-2 through an ObR-dependent JAK2/STAT3 signaling pathway.

Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer

“…These complex mechanisms are important for studying the behavior and the roles of tTJ proteins in cancers. Leptin promotes human endometriotic cell migration and invasion34. We previously reported that, in Sawano cells, a decrease of LSR expression induced by leptin and an increase of it induced by adiponectin and AMPK activators of the drugs for type 2 diabetes metformin and berberine, were observed and that the AMPK activators prevented cell migration and invasion induced by loss of LSR by leptin treatment16.…”

Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient Min Mice

“…In the present study, we found that Mest, which has been reported to be an inhibitory factor of Wnt signaling [38] and has been upregulated in obese adipose tissue [51], was significantly elevated in colorectal tumors of Min/OPN(−/−) mice. It has been reported that leptin, an obesity-related factor, upregulates MMP-2 [52] and induces EMT [53]. As a bone marker, OPN is inversely associated with leptin in non-diabetic women [54].…”

The role of epigenetic changes in preeclampsia

“…MMP‐2 gene is a necessary member of MMP family and has a role in regulation of migration of different cells including, cervical cancer, trophoblast cells, and endometriosis cells . The amount of miR‐517‐5p expression was high in PE and this caused inhibited invasive and proliferative of JAR cells in placenta of PE patients .…”