Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2 complex

Shou P Guan1, Alan T L Lam1,2, Jennifer P Newman1,3

  • 1Laboratory of Cancer Gene Therapy, Cellular and Molecular Research Division Humphrey Oei Institute of Cancer Research National Cancer Center Singapore Singapore.

FEBS Open Bio
|January 12, 2018
PubMed

Insights

Matrix metalloproteinase-1 (MMP-1) secreted by human mesenchymal stem cells (MSCs) cleaves the insulin-like growth factor-2 (IGF-2)/IGF-binding protein 2 (IGFBP2) complex. This releases free IGF-2, enhancing MSC migration toward tumors.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Cancer Research

Background:

  • The tumor tropism of human mesenchymal stem cells (MSCs) is not fully understood.
  • Previous work linked MSC migration potential to matrix metalloproteinase (MMP)-1 expression and activity.
  • Highly tumor-tropic MSCs exhibit elevated levels of MMP-1 and insulin-like growth factor (IGF)-2.

Purpose of the Study:

  • To investigate the functional roles of IGF-2 and MMP-1 in mediating MSC tumor tropism.
  • To elucidate the mechanism by which MMP-1 influences MSC migration in a tumor microenvironment.

Main Methods:

  • Assessing the effect of exogenous recombinant IGF-2 and MMP-1 on MSC migration.
  • Analyzing the correlation between IGF-2, MMP-1 expression, and MSC migratory capacity.
  • Testing the hypothesis that MMP-1 cleaves IGF-2/IGF-binding protein 2 (IGFBP2) complexes.
  • Evaluating conditioned media from high-migration MSCs for IGF-2/IGFBP2 complex cleavage activity.

Main Results:

  • Both recombinant IGF-2 and MMP-1 stimulated MSC migration.
  • A positive correlation was observed between IGF-2, MMP-1 expression, and MSC migration.
  • Conditioned media from highly migrating MSCs, rich in MMP-1, effectively cleaved the IGF-2/IGFBP2 complex.
  • This cleavage released free IGF-2, suggesting a role in facilitating MSC migration.

Conclusions:

  • MMP-1 secreted by highly tumor-tropic MSCs plays a crucial role in tumor tropism.
  • MMP-1 facilitates MSC migration by cleaving the IGF-2/IGFBP2 complex, releasing free IGF-2.
  • This mechanism highlights a novel pathway regulating MSC homing to tumors, with potential therapeutic implications.

Related Concept Videos

Cleavage and Blastulation01:33

Cleavage and Blastulation

After a large-single-celled zygote is produced via fertilization, the process of cleavage occurs while zygotes travel through the uterine tube. Cleavage is a mitotic cell division that does not result in growth. With each round of successive cell division, daughter cells get increasingly smaller.
50.5K
Predicting Products: SN1 vs. SN202:27

Predicting Products: SN1 vs. SN2

Nucleophilic substitution reactions of alkyl halides can proceed via an SN1 or an SN2 mechanism. While in SN2 reactions, the nucleophile attacks the substrate simultaneously as the leaving group departs, in SN1 reactions, the substrate first dissociates to give the carbocation intermediate. Various factors such as the structure of the substrate, the strength of the nucleophile, and the nature of the solvent promote one mechanism over the other.
With increased substitution on the alkyl halide,...
17.4K
Facilitated Transport01:19

Facilitated Transport

The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repels substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In  facilitated transport, also known as facilitated diffusion, molecules and ions travel across a...
152.1K
Facilitated Transport01:19

Facilitated Transport

The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repels substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In  facilitated transport, also known as facilitated diffusion, molecules and ions travel across a...
18.8K
Social Facilitation01:04

Social Facilitation

Not all intergroup interactions lead to negative outcomes. Sometimes, being in a group situation can improve performance. Social facilitation occurs when an individual performs better when an audience is watching than when the individual performs the behavior alone. This typically occurs when people are performing a task for which they are skilled.
36.6K
Facilitated Diffusion01:16

Facilitated Diffusion

The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
1.4K