Mmp-9 In Tumor Invasion And Metastasis, As Well As The Impact Of Chronic Myeloid Leukemia Bone Marrow Stromal And Hematopoietic Stem Cell Adhesion Mechanism

Matrix metalloproteinases (MMPs), a family of zinc-dependent proteinases, have the ability to degrade extracellular matrix components. They take an active part in multiple physiological and pathological processes including inflammation, embryo development, angiogenesis, tumor invasion and metastasis. Matrix metalloproteinases are abnormally expressed by a variety of solid tumors and hematopoietic malignancies and play an important role in tumor invasion and metastasis through extracellular matrix degradation. One number of MMPs family, MMP-9 plays a critical role in tumor invasion and metastasis. In the first part, downregulation by RNA interference decreased the capacity of MMP-9 to induce cell invasion and migration, but promoted cell adhesion in human fibrosarcoma cell line HT1080. Upon transplantation, transfected MMP-9 RNAi plasmid could effectively inhibit potency of inducing tumor in vivo. RNA interference wound provides a novel approach for anti-tumor therapy.Currently, some studies find that MMPs cleave some growth factors, adhesion molecules and their receptors, and thereby impair their activity and function, alter cell adhesion and immunological behaviors. ICAM-1 is an adhesion molecule expressed on bone marrow stromal cells and endothelial cells. It is associated with the LFA-1 expressed on hematopoietic stem cells (HSCs) and the differentiated blood cells to mediate cell adhesion. MMP-9 cleaves ICAM-1 to change it from membrane form to soluble form (s-ICAM-1). In the second part, we respectively compared the levels of MMP-9 and ICAM-I expression by mesenchymal stem cells (MSCs) from bone marrow of the healthy donors and CML patients, and s-ICAM in culture supernatant from MSCs. The results showed that MMP-9 overexpressed on CML bone marrow-derived MSCs. To investigate the mechanism of MMP-9 induced adhesion defects of CML bone marrow matrix, we analyzed the level of s-ICAM-1 in culture supernatant from untansfected and transfected MSCs, ELISA results revealed low level of s-ICAM-1 in culture supernatant from transfected MSCs. It suggested that the accelerated disease by MMP-9 due to induction of adhesion defects of bone stromal cells that alter migration of the leukemic cells.