In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy

Yoshioka, Hiroki; Yamamoto, Shinji; Hanaoka, Hirofumi; Iida, Yasuhiko; Paudyal, Pramila; Higuchi, Tetsuya; Tominaga, Hideyuki; Oriuchi, Noboru; Nakagawa, Hidewaki; Shiba, Yasuhiro; Yoshida, Kōji; Osawa, Ryuji; Katagiri, Toyomasa; Tsunoda, Takuya; Nakamura, Yusuke; Endo, Keigo

doi:10.1007/s00262-011-1186-0

Cited by 16 publications

(11 citation statements)

References 23 publications

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“…Also, in this case the research results were validated with the qRT-PCR technique. Thereby, as mentioned in the introduction, P-cadherin somewhat naturally becomes the potential target for BTC, and this was confirmed by the findings of other teams [ 29 , 31 ].…”

Section: Discussionsupporting

confidence: 67%

“…Due to their characteristics, these proteins are considered for cancer immunotherapy applications [ 30 ]. This has been recently confirmed by the newest findings presented by Yoshioka et al concerning use of yttrium-labeled antibodies in mice against CDH3 /P-cadherin (mAb-6) in CRC neoplasms and lung cancer [ 31 ]. Taking into account the already solid position of biologic targeted therapy, which at the present time is increasingly used in clinical practice and in CRC treatment, these findings are particularly interesting [ 32 ].…”

Section: Introductionmentioning

confidence: 65%

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Expression Level of Genes Coding for Cell Adhesion Molecules of Cadherin Group in Colorectal Cancer Patients

et al. 2015

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BackgroundColorectal Cancer (CRC) is one of the most frequently diagnosed neoplasms and also one of the main death causes. Cell adhesion molecules are taking part in specific junctions, contributing to tissue integrality. Lower expression of the cadherins may be correlated with poorer differentiation of the CRC, and its more aggressive phenotype. The aim of the study is to designate the cadherin genes potentially useful for the diagnostics, prognostics, and the treatment of CRC.Material/MethodSpecimens were collected from 28 persons (14 female and 14 male), who were operated for CRC. The molecular analysis was performed using oligonucleotide microarrays, mRNA used was collected from adenocarcinoma, and macroscopically healthy tissue. The results were validated using qRT-PCR technique.ResultsAgglomerative hierarchical clustering of normalized mRNA levels has shown 4 groups with statistically different gene expression. The control group was divided into 2 groups, the one was appropriate control (C1), the second (C2) had the genetic properties of the CRC, without pathological changes histologically and macroscopically. The other 2 groups were: LSC (Low stage cancer) and HSC (High stage cancer). Consolidated results of the fluorescency of all of the differential genes, designated two coding E-cadherin (CDH1) with the lower expression, and P-cadherin (CDH3) with higher expression in CRC tissue.ConclusionsThe levels of genes expression are different for several groups of cadherins, and are related with the stage of CRC, therefore could be potentially the useful marker of the stage of the disease, also applicable in treatment and diagnostics of CRC.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 65%

Expression Level of Genes Coding for Cell Adhesion Molecules of Cadherin Group in Colorectal Cancer Patients

et al. 2015

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“…However, using a quantitative approach, increased promoter hypomethylation was identified in only 77% of carcinomas (15), which does not account for the universal upregulation of the expression of this gene in AD and cancer. P-cadherin has also been used as a target for immunotherapy in the treatment of AC (16).…”

Section: Discussionmentioning

confidence: 99%

Expression changes of cell-cell adhesion-related genes in colorectal tumors

et al. 2015

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Abstract. Epithelial tissues achieve a highly organized structure due to cell-cell junction complexes. Carcinogenesis is accompanied by changes in cell interactions and tissue morphology, which appear in the early stages of benign tumors and progress along with invasive potential. The aim of the present study was to analyze the changes in expression levels of genes encoding intercellular junction proteins that have been previously identified to be differentially expressed in colorectal tumors compared with normal mucosa samples (fold change, >2.5) in genome-wide expression profiling. The expression of 20 selected genes was assessed using quantitative reverse transcription polymerase chain reaction in 26 colorectal cancer, 42 adenoma and 24 normal mucosa samples. Between these tissue types, differences were observed in the mRNA levels of genes encoding adherens junction proteins (upregulation of CDH3 and CDH11, and downregulation of CDH19 and PTPRF), tight junction proteins (upregulation of CLDN1 and CLDN2, and downregulation of CLDN5, CLDN8, CLDN23, CLDN15, JAM2 and CGN) and desmosomes (upregulation of DSC3 and DSG3, and downregulation of DSC2), in addition to a decrease in the expression of certain other genes involved in intercellular connections: PCDHB14, PCDH7, MUPCDH and NEO1. The differences between tissue types were statistically significant, and separate clustering of normal adenoma and carcinoma samples was observed in a hierarchical clustering analysis. These results indicate that the morphological changes in neoplastic colon tissue that occur during the 'adenoma-carcinoma sequence' are accompanied by specific changes in the expression of multiple genes encoding the majority of cell-cell junction complexes. The particular differential expression patterns appear to be consistent among patients with cancer and adenoma, in addition to normal mucosa samples.

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“…Furthermore, P-cadherin upregulation is observed in gastric, lung, colorectal and pancreatic cancer patients (Imai et al, 2008;Taniuchi et al, 2005). Hence, efforts to develop therapeutic agents against P-cadherin have recently intensified (Yoshioka et al, 2012;Zhang et al, 2010;Park et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The X-ray structure of human P-cadherin EC1-EC2 in a closed conformation provides insight into the type I cadherin dimerization pathway

et al. 2015

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Cadherins are a large family of calcium-dependent proteins that mediate cellular adherens junction formation and tissue morphogenesis. To date, the most studied cadherins are those classified as classical, which are further divided into type I or type II depending on selected sequence features. Unlike other members of the classical cadherin family, a detailed structural characterization of P-cadherin has not yet been fully obtained. Here, the high-resolution crystal structure determination of the closed form of human P-cadherin EC1-EC2 is reported. The structure shows a novel, monomeric packing arrangement that provides a further snapshot in the yet-to-be-achieved complete description of the highly dynamic cadherin dimerization pathway. Moreover, this is the first multidomain cadherin fragment to be crystallized and structurally characterized in its closed conformation that does not carry any extra N-terminal residues before the naturally occurring aspartic acid at position 1. Finally, two clear alternate conformations are observed for the critical Trp2 residue, suggestive of a transient, metastable state. The P-cadherin structure and packing arrangement shown here provide new and valuable information towards the complete structural characterization of the still largely elusive cadherin dimerization pathway.

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In vivo therapeutic effect of CDH3/P-cadherin-targeting radioimmunotherapy

Abstract: Our findings demonstrate that CDH3/P-cadherin-targeting RIT with (90)Y-MAb-6 is a promising strategy for the treatment for cancers expressing CDH3/P-cadherin.

Cited by 16 publications

References 23 publications

Expression Level of Genes Coding for Cell Adhesion Molecules of Cadherin Group in Colorectal Cancer Patients

Expression Level of Genes Coding for Cell Adhesion Molecules of Cadherin Group in Colorectal Cancer Patients

Expression changes of cell-cell adhesion-related genes in colorectal tumors

The X-ray structure of human P-cadherin EC1-EC2 in a closed conformation provides insight into the type I cadherin dimerization pathway

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