Abstract
BackgroundThrombospondin-1 (TSP-1) is an extracellular matrix component glycoprotein, which is known to be a potent inhibitor of angiogenesis and may be important in cancer invasiveness. We examined the TSP-1 expression in correlation with conventional clinicopathological parameters to clarify its prognostic significance in bladder cancer. In addition, the possible correlation of TSP-1 expression with microvessel count, VEGF expression, p53 expression as well as with the expression of the extracellular matrix components was studied to explore its implication in vascularization and tumour stroma remodeling.MethodsThe immunohistochemical expression of TSP-1 in tumour cells and in the tumour stroma was studied in 148 formalin-fixed paraffin-embedded urothelial cell carcinoma tissue samples.ResultsTSP-1 was detected in perivascular tissue, at the epithelial-stromal junction, in the stroma and in tumour cells in the majority of the cases. In tumour cells, low TSP-1 expression was observed in 43% of the cases, moderate and high in 7%, while 50% showed absence of TSP expression. A higher TSP-1 immunoreactivity in well and moderately differentiated tumours compared to poorly differentiated was noted. PT1 tumours showed decreased TSP-1 expression in comparison to pTa and pT2–4 tumours. Increased tumour cell TSP-1 expression was related to increased microvessel density. In the tumour stroma, 37% of the cases showed small amount of TSP-1 expression, 7.5% moderate and high, while 55% of the cases showed absence of TSP-1 stromal immunoreactivity. Stromal TSP-1 expression was inversely correlated with tumour stage and tumour size. This expression was also positively correlated with microvessel density, VEGF expression and extracellular matrix components tenascin and fibronectin. Using univariate and multivariate analysis we didn't find any significant correlation of TSP-1 expression in superficial tumours in both tumour cells and tumour stroma in terns of the risk of recurrence and disease progressionConclusionOur data suggest that both tumour and stromal TSP-1 expression may play a role in tumour aggressiveness and angiogenesis. In addition, the correlation of stromal TSP-1 expression with extracellular matrix components fibronectin and tenascin indicate its possible implication in tumour stroma remodeling.
Highlights
Thrombospondin-1 (TSP-1) is an extracellular matrix component glycoprotein, which is known to be a potent inhibitor of angiogenesis and may be important in cancer invasiveness
TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in tumour cells (Fig. 1) in the majority of the cases
Larger tumours (>3 cm) showed higher stromal TSP-1 expression (p = 0.021) (Table 2). This expression was positively correlated with MVD (p = 0.031) and vascular endothelial growth factor (VEGF) expression (p = 0.001) as well as with both extracellular matrix components tenascin (p < 0.0001) and fibronectin. (p = 0.003) (Table 3)
Summary
Thrombospondin-1 (TSP-1) is an extracellular matrix component glycoprotein, which is known to be a potent inhibitor of angiogenesis and may be important in cancer invasiveness. Thrombospondins (TSPs) are a family of extracellular proteins recognized as an endogenous constituent of the extracellular matrix (ECM) in many human tissues. They are adhesive proteins that promote cell-cell and cellmatrix interactions [1]. Each representing a separate gene product, probably exist in most vertebrate species. Each of these five proteins has a specific pattern of expression in embryonic and adult tissues with most tissues expressing at least one family member. TSP has implicated in the regulation of cell growth and proliferation [6], cell motility [7,8] cytosceletal organization [9], inflammation and wound healing [10], and the development and differentiation of cell types [11,12]
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