Myoepithelial cells in situ and in vitro exert important paracrine effects on
carcinoma cells which are mediated by high expression of extracellular matrix molecules,
proteinase inhibitors and
angiogenic inhibitors. Myoepithelial xenografts (human matrix secreting (HMS)-X, HMS-3X and HMS-4X) established from benign human salivary gland and breast
myoepithelial tumors accumulate an abundant extracellular matrix which can be extracted with 6 M
urea and 2 M
guanidinium hydrochloride to form a gel at 25-37 degrees C. This gel, termed
Humatrix, exhibits different biochemical and
biological properties than the conventional non-human matrical
gels in existence, i.e.
Matrigel and
Vitrogen 100. Whereas
Matrigel consists mainly of basement membrane molecules, e.g.
laminin,
type IV collagen and
heparan sulfate proteoglycan, and
Vitrogen 100 consists mainly of non-basement membrane molecules, e.g. type I and
type III collagen,
Humatrix contains significant amounts of both basement membrane and non-basement membrane molecules, including large amounts of
chondroitin sulfate proteoglycan. Like
Matrigel,
Humatrix contains bound
growth factors, including
epidermal growth factor (
EGF) and
insulin-like growth factor-I (
IGF-I); unlike
Matrigel, which contains predominantly significant quantities of bound
proteinases, including
tissue-type plasminogen activator (tPA),
matrix metalloproteinase (MMP)-2 and MMP-9, and angiogenic factors, including
basic fibroblast growth factor (bFGF) and
transforming growth factor (
TGF)-beta,
Humatrix contains predominantly bound
proteinase inhibitors such as
protease nexin II (PN-II) and alpha1-antitrypsin and
angiogenic inhibitors such as thrombospondin-1.
Humatrix selectively stimulates the growth and tumorigenicity of human myoepithelial cell lines but inhibits invasion, angiogenesis and
metastasis of other non-myoepithelial malignant cell lines. Because of its myoepithelial origin
Humatrix represents a more natural source of extracellular matrix molecules and bound factors that
carcinoma cells encounter in vivo.