CD70: a new tumor specific biomarker for renal cell carcinoma.
ABSTRACT To date there have been no specific tumor markers available for the differential diagnosis of renal cell carcinoma (RCC). In an earlier study we identified high RNA expression of CD70 in clear cell RCC. CD70 is a type II transmembrane protein belonging to the tumor necrosis factor family. It represents the ligand for CD27, a glycosylated transmembrane protein of the tumor necrosis factor receptor family. To our knowledge the function of CD70 in solid tumors is not known. In the current study we analyzed CD70 protein expression in different RCC subtypes.
A total of 68 tumor samples of different histopathological subtypes were investigated by immunochemistry, including 41 clear cell, 19 papillary and 5 chromophobe RCCs, and 3 oncocytomas as well as their normal tissue counterparts. Immunochemistry was performed on frozen tissue samples using monoclonal antibody against CD70.
None of the normal kidney tissues showed CD70 expression. In contrast, all clear cell RCCs expressed CD70 at a high level. Positive immunostaining was observed in 1 papillary (5%) and in 1 chromophobe (20%) RCC. Five papillary tumor samples (26%) showed focal staining in less than 5% of cells. All other samples were negative for CD70.
Our study identified CD70 as a new specific tumor marker for clear cell RCC. This new marker can be used for differential diagnosis in cases of uncertain histological classification. The function of this protein in tumorigenesis and its use as a diagnostic marker in serum and urine or as a therapeutic tool must be investigated in further studies.
- SourceAvailable from: Ferdinand von Eggeling
[Show abstract] [Hide abstract]
- "One confirmed way for RCC to induce apoptosis in lymphocytes is through FasL expression . Another potential immune-regulatory gene, CD70, a member of the tumor necrosis superfamily, has been identified in earlier studies to be specifically overexpressed in clear cell RCC  . "
ABSTRACT: Tumors can escape immune recognition and destruction through the induction of apoptosis in lymphocytes. Although renal cell carcinoma (RCC) is able to prevent immune recognition, only a few genes (such as FasL) that are relevant for RCC immune escape have been identified so far. We have previously shown that some apoptosis-inducing genes are overexpressed in RCC. We hypothesized that these genes could be part of the immune-escape strategy of these tumors. Here we report that CD70, a cytokine overexpressed in RCC, promotes lymphocyte apoptosis through interaction with its receptor CD27 and with the intracellular receptor-binding protein SIVA. Apoptosis increased after cocultivating lymphocytes with the RCC cell lines A498 and CAKI2. The addition of recombinant soluble CD70 to both native lymphocytes and a T-cell cell line resulted in increased lymphocyte apoptosis as well. Furthermore, induced apoptosis could be partially blocked with anti-CD27 and anti-CD70 antibodies. Our results strongly indicate a role for CD70 and CD27 receptor in lymphocyte apoptosis within the tumor environment. Apoptosis mediated by exposure to the CD70 secreted by tumor cells may contribute to the failure of RCC patients to develop an effective lymphocyte-mediated antitumor response.Neoplasia (New York, N.Y.) 12/2006; 8(11):933-8. DOI:10.1593/neo.06451 · 5.40 Impact Factor
[Show abstract] [Hide abstract]
- "Our studies showed a high-level expression of CD70 on RCC cells that might be expected to induce a strong immune response against the tumour. Frequent expression of CD70 on RCC was recently also reported by Junker et al (2005). Although RCC is known to be a highly immunogenic tumour, it is also a very aggressive cancer that is clearly able to escape immune surveillance . "
ABSTRACT: In order to identify potential markers of renal cancer, the plasma membrane protein content of renal cell carcinoma (RCC)-derived cell lines was annotated using a proteomics process. One unusual protein identified at high levels in A498 and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally expressed on a subset of B, T and NK cells, where it plays a costimulatory role in immune cell activation. Immunohistochemical analysis of CD70 expression in multiple carcinoma types demonstrated strong CD70 staining in RCC tissues. Metastatic tissues from eight of 11 patients with clear cell RCC were positive for CD70 expression. Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody-receptor complex. Coincubation of the internalising anti-CD70 antibody with a saporin-conjugated secondary antibody before addition to A498 cells resulted in 50% cell killing. These data indicate that CD70 represents a potential target antigen for toxin-conjugated therapeutic antibody treatment of RCC.British Journal of Cancer 09/2006; 95(3):298-306. DOI:10.1038/sj.bjc.6603222 · 4.82 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Biomarkers in the clinical oncology field can have tremendous therapeutic impact especially if the marker is detected before clinical symptoms. This impact can be extended to the evaluation of clinical oncology treatments allowing evaluation of potential compounds to determine their efficacy in the disease treatment. The discovery of clinical biomarkers can consume time, resources and costs. Therefore, it is important that the most effective strategies are employed to discover these biomarkers. These strategies may include the integration of available genomic, proteomic and histopathological technologies, which could reduce the costs and aid in the validation of the biomarker. Certainly the type of biomarker needed to address a particularly defined problem will drive the type of technology. However, a single biomarker to diagnose a specific cancer can be as elusive as relying on a single technology. This review examines some of the technologies used to discover biomarkers and presents the use of combinatorial technical synergies to discover and validate potential clinical oncology biomarkers.Current Topics in Medicinal Chemistry 02/2005; 5(11):1047-51. DOI:10.2174/156802605774297074 · 3.45 Impact Factor