BACKGROUND Osteopontin (OPN) is a cytokine associated with a cell-matrix via integrins. Fibroblast specific protein-1 (FSP-1), known as S100A4, has been implicated in cell migration by non-muscle myosin. We investigated whether the role of OPN and FSP-1/S100A4 expression in their contribution to the podocyte phenotype change to form podocyte bridge and cellular crescent. METHODS Glomerular expression of OPN and FSP-1/S100A4 in renal biopsies of 16 patients with crescentic glomerulonephritis (CrGN) and 13 normal renal biopsies were studied by immunohistochemistry. RESULTS The expression of OPN and FSP-1/S100A4 was increased in the podocytes of glomeruli, with and without crescents, in patients with CrGN. Neither OPN nor FSP-1/S100A4 was expressed in glomeruli from the normal controls (p<0.01). A significant positive correlation was found between the expression of OPN in glomerular tufts and cellular crescents, and the expression of OPN and FSP-1/S100A4 in glomerular tufts (p<0.05). CONCLUSIONS The results suggest that OPN plays a role in early podocyte attachment to Bowman's capsule, and FSP-1/S100A4 potentiate podocyte contribution to cellular crescent formation by inducing cellular migration and growth.
BACKGROUND Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement. METHODS Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry. RESULTS OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls. CONCLUSIONS The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.
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Podocyte Expression of Osteopontin and FSP-1/S100A4 in Human Crescentic Glomerulonephritis Ghil Suk Yoon, Tae Sook Kim The Korean Journal of Pathology.2011; 45(3): 237. CrossRef
BACKGROUND Metastasis is one of the most important characteristics of cancer in terms of its impact on patient survival. Unfortunately, identification of altered genes during tumor metastasis is limited. METHODS Using high-throughput microarrays containing 19K spotted human oligonucleotides, gene expression of primary and matched metastatic colon cancer were compared in previous study. Although DNA microarray analysis did not demonstrate complete classification of primary and metastatic carcinoma, 80 differentially expressed genes were identified. Among these, expression of osteopontin, matrix metalloproteinase-1 (MMP-1) and serpin A1 was assessed using immunohistochemistry in a validation set containing 43 pairs from tissue microarrays. RESULTS The expression of osteopontin was significantly higher in metastatic carcinoma than in primary carcinoma, as indicated by mRNA expression. The expression of MMP-1 was significantly lower in metastatic carcinoma. Expression of serpin A1 was not correlated with the microarray results. CONCLUSIONS Osteopontin and MMP-1 expression successfully classified primary and metastatic colorectal carcinomas and further studies on their clinical application is encouraged.
BACKGROUND Osteopontin (OPN) is a glycoprotein and it participates in cell-cell and cell-matrix interactions. In vitro studies suggest that the OPN expression is associated with tumor metastasis, and especially with the metastasis of osteotropic tumors originating in breast, prostate and lungs. Since no human tissue study has suggested the means by which OPN participates in the tumorigenesis, angiogenesis, progression and metastasis of renal cell carcinoma (RCC), we evaluated the expression and prognostic significance of OPN in RCC. METHODS Immunohistochemistry was performed with using the primary antibody for OPN on the archival paraffin-embedded tissue microarray specimens from 51 RCC patients who underwent radical or simple nephrectomy. RESULTS In the normal kidney specimens, OPN was expressed in a few compressed distal tubules adjacent to the RCCs. In RCCs, the OPN expression was elevated in larger tumors (p<0.05) and in the tumor with low microvessel density (p<0.01). In the present study, univariate analysis indicated that stage, tumor size, lymph node and distant organ metastasis are significant prognostic factors for disease free survival (DFS) in RCC patients (p<0.01), but OPN is not (p=0.0661). Multivariate analysis indicated lymph node metastasis is the independent prognostic indicator of DFS (p<0.05). CONCLUSION Though this study has statistical limitations, these results suggest OPN plays a role in tumor progression and metastasis and it may act as a potential prognostic indicator to predict the prognosis of RCC patients.
Background : The expressions of osteopontin (OPN), zonula occludens-1 (ZO-1) and E-cadherin, known as cell adhesion-associated substances, were examined in adenoma and adenocarcinoma of the colon. The relationship of their expressions with clinicopathologic factors was examined to investigate the roles of these proteins in the development, invasion or metas- tasis of colon adenocarcinoma. Methods : The expressions of OPN, ZO-1, and E-cadherin were examined in 54 cases of adenoma and 67 cases of adenocarcinoma of the colon by immunohistochemical staining. Results : The expression of OPN in colon adenocarcinoma correlated with staging (p=0.012) and distant metastasis (p=0.021). The expression of ZO-1 was closely related with tumor cell differentiation (p<0.001), and the reduced expression of E-cadherin was associated with tumor cell differentiation (p=0.05) and lymph node metastasis (p<0.001). Co-expression of ZO-1 and E-cadherin was significantly associated with tumor cell differentiation, and the expressions of ZO-1 and E-cadherin were reduced or lost in all cases (5 cases) of poorly differentiated adenocarcinoma. Conclusions : Our data suggest that OPN is involved in the process of invasion and metastasis of colon adenocarcinoma, and ZO-1- and E-cadherin-mediated cell adhesion may play an important role in the differentiation of colon adenocarcinoma.