CLEAR CELLS RENAL CARCINOMA: THE ROLE OF PROTEIN BMP7 AND ITS DIFFERENTIAL EXPRESSION

OLEA, GB.; MELANA COLAVITA, JP; BARNES,T; RODRIGUEZ,JP.; DELFINO, MI; LOMBARDO, DM.; AGUIRRE, MV.

Buenos Aires

Encuentro; XX ANNUAL MEETING OF THE ARGENTINEAN BIOLOGY SOCIETY (SAB); 2018

Argentinean Biology Society

The complex biology of the ccRCC, added to its unpredictable clinical behavior, highlights the need to determine other biomarkers to evaluate neoplastic progression, as well as to generate new therapeutic alternatives taking into accounts the intratumoral heterogeneity. Bone morphogenetic proteins (BMPs) regulate diverse cellular processes, such as proliferation, differentiation, and apoptosis. Among the BMPs isoforms, BMP 7 has been studied in several cancers, but thus far contradictory results have been obtained. This study aimed to clarify the role and significance of BMP7 expression in ccRCC. We performed a study of BMP 7 expression in surgical renal ccRCC samples and in the human renal carcinoma cell line Caki-2 by immunohistochemistry and immunocytochemistry, respectively. Proliferation was evaluated with Ki-67. Tumor samples were collected from patients diagnosed with ccRCC who underwent radical or partial nephrectomy. The clinical-pathological evaluation was performed at the Pathological Anatomy Service of the Hospital J.R. Vidal (Corrientes). Sections of 4 μm of ccRCC tumors and normal adjacent kidney tissue were included in paraffin and placed on silanized slides. Additionally, Caki-2 cells (ATCC® HTB-47?) were cultured on cover glasses, and they were fixed with methanol (99,8 %) for 1 min and were kept until use for BMP7 detection by immunocytochemistry. The conditions for antigen retrieval and the incubation with the BMP-7 antibody (Santa Cruz Biotechnology, 1:200) were adjusted. BMP7 was differentially expressed between the core and periphery regions. Immunoreactions occurred mainly at the perinuclear level, and it was related to the pathological stage and nuclear grade. BMP7 expression was lower in controls. This study reveals that BMP7 is overexpressed in ccRCC samples according to the degree of invasiveness and pathological stages compared to control distal samples. BMP7 expression in CAKI-2 confims a perinuclear pattern similar to cells ccRCC. This preliminary data aims us to design future studies through qPCR and other molecular biology techniques for comparing BMP7 expression with other potential biomarkers such as the pluripotential protein OCT4, in search of tumor stem cells identification.