Related Experiment Video

Updated: Apr 26, 2026

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis

Published on: November 8, 2024

Activin A, B, and AB increase human trophoblast cell invasion by up-regulating N-cadherin

Yan Li¹, Christian Klausen, Jung-Chien Cheng

¹Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.

The Journal of Clinical Endocrinology and Metabolism

|August 9, 2014

Context:

Inhibin β-subunits and activin receptors are expressed by human trophoblast cells. Although activin A has been shown to enhance human trophoblast cell invasion, whether two additional activin isoforms, activin B and AB, exert similar effects remains unknown. Moreover, whether the expression of mesenchymal adhesion molecule neural cadherin (N-cadherin) is essential for this proinvasive effect of activin has yet to be determined.

Objective:

To examine the effects of all three activin isoforms on human trophoblast cell invasion and the involvement of N-cadherin.

Design:

HTR8/SVneo immortalized extravillous cytotrophoblast cells and primary cultures of human extravillous cytotrophoblast cells were used as study models. Small interfering RNA-mediated knockdown approaches were used to investigate the molecular determinants of activin-mediated functions.

Setting:

An academic research center.

Main Outcome Measures:

Reverse transcription-quantitative real-time PCR and Western blot analysis were used to examine mRNA and protein levels, respectively. Cell invasiveness was assessed by Matrigel-coated transwell assays.

Results:

All three activin isoforms produced comparable increases in HTR8/SVneo cell invasion as well as N-cadherin expression. In addition, the up-regulatory effect of activin isoforms on N-cadherin was confirmed in primary cultures of human trophoblast cells. Interestingly, small interfering RNA-mediated down-regulation of N-cadherin attenuated basal and activin-induced invasion of both HTR8/SVneo and primary trophoblast cells. All three activin isoforms induced equivalent phosphorylation of SMAD2 and SMAD3. Importantly, activin-stimulated cell invasion, up-regulation of N-cadherin, as well as activation of SMAD2/SMAD3 were abolished by the TGF-β type I receptor inhibitor SB431542 in HTR8/SVneo cells. Furthermore, knockdown of SMAD2/3 or common SMAD4 abolished the stimulatory effects of all three activin isoforms on N-cadherin expression.

Conclusion:

Activin A, B, and AB produce comparable increases in human trophoblast cell invasion by up-regulating N-cadherin expression in a SMAD2/3-SMAD4-dependent manner.

More Related Videos

In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines

In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-trimester Trophoblast Cell Lines

Published on: March 5, 2019

A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta

A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta

Published on: September 27, 2017

Related Concept Videos

Cadherins in Tissue Organization

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...

Intracellular Signaling Affects Focal Adhesions

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...

Tension Response at Adherens Junctions

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...

Adherens Junctions

Adherens Junctions

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic

Cancer Cell Migration through Invadopodia

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...

Activation of Integrins

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...

Articles linked to this work by shared authors, journal, and citation graph.

Growth differentiation factor myostatin regulates epithelial-mesenchymal transition genes and enhances invasion by increasing serine protease inhibitors E1 and E2 in human trophoblast cells.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology·2023

Interleukin-1β and plasminogen activating system members in endometriotic stromal cell migration/invasion.

F&S science·2022

Characterization of the roles of amphiregulin and transforming growth factor β1 in microvasculature-like formation in human granulosa-lutein cells.

Frontiers in cell and developmental biology·2022

Activin A promotes hyaluronan production and upregulates versican expression in human granulosa cells†.

Biology of reproduction·2022

Myostatin increases human trophoblast cell invasion by upregulating N-cadherin via SMAD2/3-SMAD4 signaling†.

Biology of reproduction·2022

Dysregulated BMP2 in the Placenta May Contribute to Early-Onset Preeclampsia by Regulating Human Trophoblast Expression of Extracellular Matrix and Adhesion Molecules.

Frontiers in cell and developmental biology·2021

See all related articles