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Published on: June 9, 2020
Differential expression pattern of annexin A2 during nephrogenesis and kidney carcinoma
Roshni Sadashiv1, Balappa Murgappa Bannur, Praveenkumar Shetty
1Department of Biochemistry, K.S. Hegde Medical Academy, Nitte University Center for Science Education and Research, Nitte University, Mangalore, Karnataka, India; shettybp@hotmail.com.
Abstract:
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.
Insights
Annexin A2 (AnxA2) expression in developing kidneys mirrors its reappearance in renal cell carcinoma (RCC). This suggests AnxA2 deregulation during tumorigenesis plays a key role in kidney cancer progression.
Area of Science:
- Oncology
- Developmental Biology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) arises from embryonic kidney cells, with diverse phenotypes linked to nephron origins.
- Annexin A2 (AnxA2), a calcium-regulated protein, is found in some renal neoplasms.
- Understanding AnxA2's role in kidney development and cancer is crucial for comprehending RCC pathogenesis.
Purpose of the Study:
- To investigate the ontogeny of AnxA2 expression during renal development.
- To compare AnxA2 expression in fetal kidneys, adult kidneys, and RCCs.
- To elucidate the role of AnxA2 in renal tumorigenesis and cancer progression.
Main Methods:
- Immunohistochemistry was used to evaluate AnxA2 immunoexpression.
- Tissue samples included autopsied fetal kidneys, normal adult kidneys, and renal cancer specimens.
- Expression patterns were analyzed across different developmental stages and in neoplastic tissues.
Main Results:
- Moderate membranous AnxA2 expression was observed in fetal ureteric buds and collecting tubules, and adult collecting ducts.
- AnxA2 was minimally expressed in adult proximal convoluted tubules but present in fetal ones, a potential origin of RCC.
- Strong membranous AnxA2 reappearance was noted in clear cell carcinoma, indicating gene deregulation.
Conclusions:
- AnxA2 immunoexpression patterns during renal development and in RCC suggest its involvement in tumorigenesis.
- Deregulation of AnxA2 during cancer development is implicated in RCC progression.
- AnxA2's specific function and altered expression highlight its decisive role in renal carcinoma pathogenesis.
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