Type 3 Repeats of Thrombospondin-2 Increases Metastasis in Mouse Colorectal Cancer CT-26 Cells

Thrombospondins (TSPs) are secreted multimeric glycoproteins that modulate extracellular matrix structure and cell behaviour. TSPs are involved in platelet aggregation, cell adhesion, migration, angiogenesis, wound healing, and proliferation. The purpose of this study was to investigate the function of TSP-2 on the invasion and migration of CT-26, and to determine the domain that is responsible for these functions. The antisense cDNA of TSP-2 was transfected to CT-26 (CT-26/AS-pREP4), which underexpressed TSP-2. Reduction of TSP-2 expression resulted in decreased activity, and decreased expression of the plasminogen/plasmin system. All of which resulted in decreased invasion and migration in vitro. The panels of murine TSP-2 cDNA subunits in CT-26/AS-pREP4 were established. The transfectants containing type 3 repeats domain revealed an increased in vitro invasion and migration, and increased pulmonary metastasis when inoculated into the tail vein of a syngenic mouse. The type 3 repeats domain was both integrin αvβ3 and phosphatidylinositol (PI) 3-kinase/Akt dependent. These findings may be useful for the development of therapeutic interventions that block either integrin αvβ3 or PI 3-kinase dependent Akt phosphorylation, resulting in the reduction of plasminogen/plasmin system and consequently block cell invasion, migration, and metastatic spread of colon cancer cells.