Specificity analysis of mouse monoclonal antibodies defining cell surface antigens of human renal cancer.

Abstract

Six mouse monoclonal antibodies (mAbs) defining separate systems of cell surface antigens of cultured human renal cancer were tested for reactivity with normal fetal and adult tissues and with neoplastic tissues. Five of the mAbs identified glycoproteins of Mr 160,000 (designated S4), Mr Mr 140,000 (F23), Mr 120,000 (S23 and S27), and Mr 115,000 (S22). The glycoprotein component of Mr 120,000 has been shown recently to be the adenosine deaminase binding protein (ADA-BP) and mAbS23 and mAbS27 define two distinct epitopes on ADA-BP. S22 was not detected on any normal fetal or adult tissues but was found on a subset of renal cancers. S4, F23, S23, and S27 defined distinct domains of the nephron: glomerulus (S4), proximal tubules (S4, F23, S23, and S27), and portions of Henle's loop (S23 and S27). mAbS4 also reacted with the interstitial matrix in the renal medulla and of other tissues, and mAbF23 reacted with fetal and adult fibroblasts. The S23 epitope of ADA-BP was expressed by placental trophoblasts and epithelial cells of breast, prostate, lung, and colon, whereas the S27 epitope was detected on a more limited range of cell types (trophoblasts and prostate epithelium). A panel of 20 renal cell carcinomas was typed for expression of these antigens; 7 phenotypes could be distinguished, with the S4+/F23+/S23+/S27+/S22+ or - phenotype (15 cases) being most common. The other antigenic system, V1, identified a heat-stable antigen that was widely expressed on cultured cell types but showed a restricted pattern of reactivity in tissues. V1 expression was limited to the adrenal cortex, Leydig cells, and the theca of ovarian follicles, and to adrenal cortical carcinomas.

Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A.

“…In contrast, we have detected gpl60 expression in most cultured and noncultured RCCs (2,5,6), suggesting that APA is a kidney differentiation antigen and not related to transformation. Similarly, murine APA (BP-1/C63) in pre-B lymphocytes is believed to define a differentiation stage unrelated to malignant potential (47).…”

“…gpl60 was isolated from normal human kidney, which expresses high levels of this protein (1,2), by first enriching for glycoproteins with lectin chromatography followed by immunoaffinity purification using anti-gpl60 mAb S4. A comparison of the amino acid sequences of three gpl60 tryptic peptides to those in the translated GenBank data base (23) revealed incomplete homology to the BP-1/6C3 differentiation antigen (24), a murine early B-lymphocyte cell surface glycoprotein.…”

“…However, despite the fact that virtually all renal cell carcinomas (RCCs) derive from proximal tubule cells (2,3), w20% of RCCs lack gpl60 expression (2,4,5). This observation indicates an altered regulation or other defect of this glycoprotein upon malignant transformation of the proximal tubule cell.…”

Cytokeratin 18 expression pattern correlates with renal cell carcinoma progression: Relationship with Snail

“…Although to date, a small number of possible marker genes are known to predict RCC behavior more accurately, a reliable marker for early diagnosis of RCC has not been reported (15). Since RCC is believed to arise from proximal tubule epithelium (16,17) and in order to identify new prognosis markers for clear cell RCC, we have examined in the present study the relationship between CK18 and Snail expression in RCC. Our findings point to the existence of a relationship between CK18 and RCC progression as well as a role for Snail during this process.…”

Regulation of aminopeptidase A expression in cervical carcinoma: role of tumor–stromal interaction and vascular endothelial growth factor

“…17 However, there have been few reports on APA expression and its functional significance in tumor cells. [18][19][20] We have recently demonstrated that APA was expressed in neoplastic lesions of the uterine cervix, and its expression was upregulated as the lesion progresses from cervical intraepithelial neoplasms (CIN) toward invasive squamous cell carcinomas (SCC). 21 However, the regulatory mechanisms for APA expression and its functional role in the progression of cervical carcinoma remain to be clarified.…”