Kedeshian P, Sternlicht M D, Nguyen M, Shao Z M, Barsky S H
Department of Pathology, UCLA School of Medicine, Los Angeles, CA 90024, USA.
Cancer Lett. 1998 Jan 30;123(2):215-26. doi: 10.1016/s0304-3835(97)00429-1.
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.
原位和体外培养的肌上皮细胞对癌细胞发挥重要的旁分泌作用，这种作用由细胞外基质分子、蛋白酶抑制剂和血管生成抑制剂的高表达介导。从人良性唾液腺和乳腺肌上皮肿瘤建立的肌上皮异种移植瘤（人基质分泌（HMS）-X、HMS-3X和HMS-4X）积累了丰富的细胞外基质，可用6M尿素和2M盐酸胍提取，并在25-37℃形成凝胶。这种凝胶称为Humatrix，与现有的传统非人类基质凝胶，即基质胶和维特胶原100相比，具有不同的生化和生物学特性。基质胶主要由基底膜分子组成，如层粘连蛋白、IV型胶原和硫酸乙酰肝素蛋白聚糖，维特胶原100主要由非基底膜分子组成，如I型和III型胶原，而Humatrix含有大量的基底膜和非基底膜分子，包括大量的硫酸软骨素蛋白聚糖。与基质胶一样，Humatrix含有结合的生长因子，包括表皮生长因子（EGF）和胰岛素样生长因子-I（IGF-I）；与基质胶不同，基质胶主要含有大量结合的蛋白酶，包括组织型纤溶酶原激活剂（tPA）、基质金属蛋白酶（MMP）-2和MMP-9，以及血管生成因子，包括碱性成纤维细胞生长因子（bFGF）和转化生长因子（TGF）-β，Humatrix主要含有结合的蛋白酶抑制剂，如蛋白酶nexin II（PN-II）和α1-抗胰蛋白酶，以及血管生成抑制剂，如血小板反应蛋白-1。Humatrix选择性地刺激人肌上皮细胞系的生长和致瘤性，但抑制其他非肌上皮恶性细胞系的侵袭、血管生成和转移。由于其肌上皮起源，Humatrix代表了癌细胞在体内遇到的更天然的细胞外基质分子和结合因子来源。
