Membrane type-1 matrix metalloproteinase promotes human melanoma invasion and growth

Joji Iida1, Krista L Wilhelmson, Matthew A Price

  • 1Department of Laboratory Medicine and Pathology, and University of Minnesota Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. iidax002@tc.umn.edu

Insights

Elevated membrane type-I metalloproteinase (MT1-MMP) expression in melanoma cells promotes selective invasion and enhances tumor growth. Inhibition of MT1-MMP blocks invasion but not motility, suggesting a key role in melanoma progression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Membrane type-I metalloproteinase (MT1-MMP) is crucial for tumor cell invasion and extracellular matrix degradation.
  • MT1-MMP is upregulated in malignant melanoma, but its precise role in tumor progression is not fully understood.

Purpose of the Study:

  • To investigate the biological consequences of elevated MT1-MMP expression in melanoma cells.
  • To evaluate the role of MT1-MMP in melanoma invasion, migration, growth, and tumorigenicity.

Main Methods:

  • Utilized the Bowes melanoma cell line to assess MT1-MMP function.
  • Examined invasion and migration across different extracellular matrix components (matrigel, type-I collagen, laminin 1, type-IV collagen).
  • Assessed 3D growth in agarose gels and matrigel, and tumorigenicity via intradermal injection. Evaluated the effect of the inhibitor BB94.

Main Results:

  • MT1-MMP expression promoted selective invasion into matrigel but not type-I collagen.
  • Melanoma cells expressing MT1-MMP showed increased migration towards laminin 1.
  • MT1-MMP enhanced 3D growth and tumorigenicity in vivo. BB94 inhibited MT1-MMP-driven invasion and growth but not motility.

Conclusions:

  • Elevated MT1-MMP expression in melanoma facilitates selective invasion and enhances tumor growth.
  • MT1-MMP plays a significant role in promoting malignant melanoma progression in vivo.
  • Targeting MT1-MMP may offer therapeutic strategies for melanoma treatment.

Related Concept Videos

The Extracellular Matrix01:42

The Extracellular Matrix

In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.Composition of the Extracellular MatrixThe extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse molecules.
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
Cancer Cell Migration through Invadopodia01:35

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, invadopodia can...
Types of Membrane Protrusions01:28

Types of Membrane Protrusions

The protrusion of the cell surface is an initial step for several cellular processes, including cell migration, phagocytosis, and neurite outgrowth. These membrane protrusions are a result of cytoskeletal rearrangement. The most  widely observed cell protrusions include lamellipodia, pseudopodia, filopodia, microvilli, invadopodia, and podosomes. These protrusions can be of two types — static or dynamic.
The microvilli, an example of stable protrusions, are finger-like projections with a...
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...