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The Extracellular Matrix (ECM)

While it is true that all living things are made of cells, that is only part of the story. Most of the cells in multicellular organisms are surrounded by a complex mixture of nonliving material that makes up the extracellular matrix (ECM). In some cases, the ECM accounts for more of the organism's bulk than its cells.

All epithelial cells as well as some other types (e.g., smooth muscle cells) are attached to a basal lamina (also known as the basement membrane) [View].

Beneath the basal lamina lies connective tissue.

Connective Tissue

The cells of connective tissue are embedded in a great amount of extracellular material. This matrix is secreted by the cells. It consists of protein fibers embedded in an amorphous mixture of huge protein-polysaccharide ("proteoglycan") molecules.

Supporting connective tissue

Gives strength, support, and protection to the soft parts of the body. The extracellular matrix of cartilage and bone is secreted by specialized cells derived from fibroblasts:

Dense connective tissue

Often called fibrous connective tissue.

Loose connective tissue

It is distributed throughout the body. It serves as a packing and binding material for most of our organs. Sheets of loose connective tissue that bind muscles and other structures together are called fascia. Collagen, elastin, and other proteins are found in the matrix.

Both dense and loose connective tissue is derived from cells called fibroblasts, which secrete the extracellular matrix.

Composition of the ECM

The ECM of vertebrates is composed of complex mixtures of

Proteins

Almost all of the proteins are glycoproteins; that is, have short chains of carbohydrate residues attached to them. (Elastin does not.) [Link to discussion of glycoproteins.]

Proteoglycans

Proteoglycans are also glycoproteins but consist of much more carbohydrate than protein; that is, they are huge clusters of carbohydrate chains often attached to a protein backbone. Some examples:

(Their presence in connective tissue like joints accounts for the popularity of N-acetylglucosamine and chondroitin sulfate as dietary supplements for arthritis sufferers.)

Proteoglycans are degraded in lysosomes. A variety of different enzymes are needed. Inherited deficiencies in any one of these produces one of some dozen different types of mucopolysaccharidosis (mucopolysaccharide is the earlier name for proteoglycan).

Syndecan-1

This proteoglycan differs from the others in being retained at the surface of the cell anchored in the plasma membrane as an integral transmembrane protein.

Syndecan-1 binds chemokines (chemotactic cytokines). When epithelia are damaged, these complexes are released and diffuse away forming a chemotactic gradient that attracts neutrophils to the site. Thus syndecan-1 plays a crucial role in inflammation.

Connecting Cells to the ECM

Most normal vertebrate cells cannot survive unless they are anchored to the extracellular matrix. This anchorage dependence is often lost when a cell turns cancerous. (HeLa cells, for example, are among the few types of vertebrate cell that can be grown in liquid culture.)

View normal mouse fibroblasts anchored to the substrate and cancerous cells that are not.

Cells attach to the ECM by means of transmembrane glycoproteins called integrins.

Cancer Metastasis

Cancers begin as a primary tumor. Most (maybe all) solid tumors shed cells into the lymph and blood. However, most of these lack the potential to develop into tumors. Eventually, however, some of the shed cells are able to take up residence and establish secondary tumors — metastases — in other locations of the body. Metastasis is what usually kills the patient.

In order to enter (and exit) the blood or lymph, cancer cells must pass through a basement membrane. They are able to do so by secreting proteinases (including serine proteases) that digest a path for them.

Link to photomicrographs with explanatory diagrams showing a lung cancer growing through the basement membrane.

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28 January 2011