Extracellular Matrix (ECM)

The extracellular matrix (ECM) surrounds and supports the cells within living systems. In mammals, the ECM is most commonly found in connective tissues such as tendon, cartilage, bone or dermis of the skin. Changes in the amount and organization of the ECM components change the type and form of the ECM. The ECM is produced and maintained by the cells that inhabit it. The proteins within the ECM can be divided into several classes based upon their structure and function within the ECM.

The most prominent class is the structural class of ECM proteins,the collagens and elastins. Collagen fibers strengthen and organize the matrix; elastin fibers provide flexibility and resilience. Other ECM proteins such as fibronectin, laminin, and tenascin allow for cell attachment and form crosslinks within the matrix gel. Finally, numerous proteoglycans and heparan sulfate-containing proteins form the highly hydrated, gel-like mixture that stabilizes the matrix within its aqueous environment.

One area of intense interest is the basement membrane surrounding the blood vessel endothelium, a thin, specialized network of ECM proteins. Composed of proteins and proteoglycans, such as collagen, laminin, entactin, fibronectin, heparin sulfate and perlecan, this membrane separates the epithelium from underlying tissues. It provides cell surface anchorage (via integrins, receptor kinases, and cell surface proteoglycans), induces cellular differentiation, gives architectural support, and limits the migration of normal cells. The ability of tumor cells to degrade the ECM components of the basement membrane and surrounding tissues is directly correlated with metastatic potential. By releasing proteolytic enzymes (e.g. MMP collagenases, plasminogen activators, cathepsins), cancer cells are able to breach the membrane and penetrate the blood vessel wall. Collagen, the primary structural element of the basement membrane and tissue scaffolding protein, represents the main deterrent in the migration of tumor cells.

	Formalin-fixed paraffin-embedded equine skin containing bovine collagen implant stained with rabbit anti-Collagen Type I (Merck cat. no. AB758) Bovine collagen = brown staining Native collagen = colorless.
	Chicken Embryonic Fibroblast cells invading out of tissue into 3D Collagen. Actin is shown in green.
	Actin cytoskeleton (red) of Cos-7 cells spread in 3D Collagen. The nucleus is shown in purple.
	Actin cytoskeleton (red) of apoptotic cells captured in 3D Collagen. The nucleus is shown in purple.
	Mouse anti-Procollagen Type I, ($ cat. no. MAB1912) staining of normal skin.
	Lumina (arrow) and invasive sprouts of HUVEC sandwiched within Fibrin gel (Merck cat. no. ECM630) and incubated for 72 hours in media supplemented with bFGF, VEGF and PMA (32X magnification).

Vitronectin

Cell migration is a fundamental function of normal cellular processes, including embryonic development, angiogenesis, wound healing, immune response, and inflammation. Cell migration is governed by a variety of factors, including cell surface adhesion receptor binding to extracellular matrix (ECM) proteins. One such matrix protein is vitronectin (VN). VN is a widely distributed high molecular weight glycoprotein found in most extracellular matrices and blood plasma that is known to promote cell adhesion and affect cell morphology, migration, differentiation, and cytoskeletal organization. Merck has a number of antibodies, purified proteins and migration assays for vitronectin related research.

SDS-PAGE and Coomassie stain using 3 mg of recombinant Vitronectin (Merck cat. no. 08-126). Arrow indicates human Vitronectin at a MW of 78kDa.)