Flow cytometric evaluation of transferrin receptor in transitional cell carcinoma

Abstract

We evaluated flow cytometric (FCM) analysis of transferrin receptor (TFR) expression as a marker for the malignant potential in transitional cell carcinoma (TCC). TCCs from 55 patients were analyzed by FCM using an anti-TFR monoclonal antibody (CD71) and a TCC-specific monoclonal antibody (EH14), which recognizes most TCC cells irrespective of the grade. The cells were divided into subpopulations according to DNA ploidy determined simultaneously. TFR expression correlated well with the grade and the stage of the tumors. TFR expression of the aneuploid tumors was significantly higher than that of the euploid tumors in all subpopulations. EH14 expression did not correlate with the grade or the stage of the tumors. EH14 expression of the aneuploid tumors was significantly higher than that of the euploid tumors in the whole cell population but not in the subpopulations. In moderately differentiated tumors or in T1 tumors, TFR expression was higher in multiple or recurrent tumors than in simple tumors. The cell size or shape were not the primary reasons for the enhanced expression of TFR in the high-grade or the high-stage tumors; instead, overproduction of TFR may take place in these tumors. Clinically, many of the TCC tumors are grouped into G2 or T1 tumors, some of which will be invasive cancers. Quantitative analysis of TFR expression using FCM may be useful to predict the prognosis of these tumors.

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers

“…Preclinical studies using intravenously administered SGT-94 showed tumor-specific targeting of bladder cancer cells in subcutaneous tumors, as well as antitumor activity in combination with chemotherapy. 13 Genitourinary tumors were treated in this study with a focus on metastatic bladder cancer, since high levels of TfR are present in human bladder cancers, especially in recurrent highgrade disease [14][15][16] making them a potential target for the SGT nanodelivery system. The plasmid within SGT-94 also included a modified cytomegalovirus (CMV) promoter which results in high expression of RB94 protein allowing RB94 protein to be detected in the cytoplasm of the cancer cell by immunochemical staining, even though RB is a nuclear protein.…”

Bioconjugate recognition molecules to quantum dots as tumor probes

“…Transferrin (Tf) and mouse anti‐human CD71 monoclonal antibody (anti‐CD71)16 are highly specific to Tf receptor/CD71 antigens on most of proliferating cells, and without cross‐reaction with other related proteins. This receptor is broadly distributed in carcinomas, sarcomas, leukemias, and lymphomas, and was reported to be associated with cell proliferation in both normal and neoplastic tissues, and thus to be used in predicting clinical behavior or response to therapy in a number of malignancies 17. Here, CdSe/ZnS QDs were synthesized from the original materials and conjugated to Tf and anti‐CD71 respectively; and then the highly photostable bioprobes were obtained with EDC and N ‐hydrocylsulfo‐succinimide (Sulfo‐NHS).…”

“…This receptor is broadly distributed in carcinomas, sarcomas, leukemias, and lymphomas, and was reported to be associated with cell proliferation in both normal and neoplastic tissues, and thus to be used in predicting clinical behavior or response to therapy in a number of malignancies. 17 Here, CdSe/ZnS QDs were synthesized from the original materials and conjugated to Tf and anti-CD71 respectively; and then the highly photostable bioprobes were obtained with EDC and N-hydrocylsulfo-succinimide (Sulfo-NHS). The efficient conjugation was verified by column filtration, Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) electrophoresis, absorption and fluorescence spectra, and circular dichroism (CD) spectrometry.…”

NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer

“…Thus, the intratumoral response to receptor-targeted therapies can be highly variable and selection pressures exerted by these therapies often result in residual treatment-resistant tumor subpopulations. Heterogeneous over-expression of tumor-associated receptors, such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2), and transferrin receptor (TfR), has been reported in a wide range of tumors, including pancreatic ductal adenocarcinoma (PDAC) [ 22 , 23 , 24 ] and head and neck squamous cell carcinoma (HNSCC) [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], in addition to breast cancers [ 33 , 34 , 35 ], ovarian cancer [ 36 , 37 ], non-small cell lung cancer [ 38 , 39 , 40 , 41 ], and bladder cancer [ 42 , 43 ]. As such, EGFR and HER-2 in particular are well-established therapeutic targets for a variety of solid tumors [ 44 , 45 , 46 , 47 , 48 , 49 , 50 ].…”