Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer.

Background The expression in the glomerular mesangial cells, papillary, and collecting duct cells demonstrated annexin A1 (AnxA1)'s role in specific renal functions. With varying concentrations of calcium (Ca2+), it is considered to regulate cellular processes such as cell proliferation, apoptosis, and clearance of apoptotic cells by forming ceramides, a key lipid mediator of apoptosis. It also participates in tumorigenesis based on its location. On account of these features, we investigated the expression of this apoptosis-associated protein in fetal kidneys at different gestational periods, mature kidneys and in kidney cancer tissues in order to localize and possibly characterize its role during nephrogenesis and renal tumors. Methods AnxA1 expression was evaluated by an immunohistochemistry technique in "paraffin-embedded" renal tissue sections from autopsied fetuses at different gestational ages, in mature kidneys and renal cancer tissues. Results The current study data demonstrated that AnxA1 is expressed in the mesangial cells and podocytes of maturing glomeruli in the developing renal cortex of fetal kidneys at 14 to 19 weeks of gestation. The expression in the mesangial cells declined in later weeks of gestation and persisted into adulthood. AnxA1 expression increased with the progression of clear cell renal cell carcinoma (CCRCC) and also in other cancer types indicating a potential role of the protein in tumorigenesis. Conclusions We presume that AnxA1 in the podocytes and mesangial cells play important roles in various signaling pathways in the functioning of the glomerulus. These results and concepts provide a framework to further dissect its biological properties and thereby develop diagnostic, prognostic, and therapeutic strategies targeting the molecule in various renal pathologies.

Differential expression pattern of annexin A2 during nephrogenesis and kidney carcinoma.

The creation of a cancer cell could be due to reactivation of repressed gene in the process of normal embryonic development. The differences in embryonic origins and functions of various components of nephron may contribute to the diversity of morphological patterns, molecular and immunohistochemical phenotypes of common renal neoplasms. Renal cell carcinomas (RCCs) are the most common amongst the genitourinary cancers. Annexin A2 (AnxA2) is a multifunctional calcium-regulated phospholipids-binding protein found in a subset of renal neoplasms. Since the tumor cells usually recapitulate embryonic cells, we studied the ontogeny of AnxA2 in developing renal tissues and compared it with those of normal adult RCCs, to better understand their role in renal development and tumorigenesis. AnxA2 immunoexpression was evaluated by immunohistochemistry from various autopsied fetuses, mature kidney and renal cancer tissue specimens. The study showed moderate membranous AnxA2 immunoexpression in the ureteric buds and collecting tubules of fetal kidneys (in all gestational ages) and in the collecting ducts of adult normal renal tissues. It is not often expressed in the proximal convoluted tubules of normal adult kidney; however, younger fetal kidneys show moderate AnxA2 immunoexpression in the proximal convoluted tubules (thought to be the origin of RCC) and the reappearance of strong membranous AnxA2 immunoexpression in the clear cell carcinoma is suggesting a deregulation of the gene during tumorigenesis. The understanding of the AnxA2 molecular immunoexpression pattern during development, its specific function and deregulated immunoexpression in different renal carcinoma types indicates the decisive role of AnxA2 in the cancer progression.