Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery

Stammes, Marieke A.; Prevoo, H.A.J.M.; Horst, Meyke C Ter; Groot, Stéphanie A.; Velde, Cornelis J.H. van de; Chan, Alan; Kuppen, Peter J. K.; Vahrmeijer, Alexander L.; Pasquale, Elena B.; Sier, Cornelis F.M.

doi:10.3390/ijms18020307

Cited by 14 publications

(5 citation statements)

References 28 publications

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“…Its expression is closely related to the degree of esophageal cancer differentiation and regional lymph node metastasis and is negatively related to clinical survival rate [ 11 ]. EPHA2 is highly expressed in breast [ 12 ], colorectal [ 13 ], esophageal [ 14 ], and prostate cancer [ 15 ]. In ovarian cancer, higher EPHA2 expression corresponds to more aggressive tumors.…”

Section: Discussionmentioning

confidence: 99%

EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway

Wang

Zhang

Cheng

2021

BioMed Research International

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EPHA2 is a member of the ephrin receptor tyrosine kinase family and is closely related to the malignant tumor progression. The effect of EPHA2 on OSCC is not clear. This study explored the role of EPHA2 and AKT/mTOR signaling pathways in Cal-27 cell invasion and migration. The expression of EPHA2 and EPHA4 in human OSCC and normal oral tissue was detected by immunohistochemistry. EPHA2-overexpressing and EPHA2-knockdown Cal-27 cells were established, and the cells were treated with an AKT inhibitor (MK2206) and mTOR inhibitor (RAD001). The expression of EPHA2 was detected by qRT-PCR, cell proliferation was evaluated by MTT assay, cell migration and invasion were examined by scratch and Transwell assay, and cell morphology and apoptosis were assessed by Hoechst 33258 staining. Western blot was performed to detect the expression of proteins related to AKT/mTOR signaling, cell cycle, and pseudopod invasion. EPHA2 and EPHA4 were highly expressed in clinical human OSCC. Overexpression of EPHA2 promoted the proliferation, migration, and invasion of Cal-27 cells, inhibited cell cycle blockage and apoptosis, and enhanced the activity of the AKT/mTOR signaling pathway. MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway

Wang

Zhang

Cheng

2021

BioMed Research International

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“…However, EphB4 is overexpressed in multiple CRC cell lines, including SW480, LIM2405 B4, and CT26 cells, highlighting its potential as a CRC biomarker ( 106 ). Differences in IHC staining for EphB4 in tumor tissue and normal tissue was very pronounced according to one team ( 48 ). IHC staining of 50 normal colon tissue samples showed EphB4 levels high in only 8% of healthy samples ( 49 ), while others showed EphB4 expression in 73% and 85.3% of clinical CRC samples ( 104 ).…”

Section: Surface Biomarkersmentioning

confidence: 99%

Beyond Colonoscopy: Exploring New Cell Surface Biomarkers for Detection of Early, Heterogenous Colorectal Lesions

et al. 2021

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Colorectal cancer (CRC) is the third leading cause of cancer-related deaths among both men and women in the United States. Early detection and surgical removal of high-risk lesions in the colon can prevent disease from developing and spreading. Despite implementation of programs aimed at early detection, screening colonoscopies fail to detect a fraction of potentially aggressive colorectal lesions because of their location or nonobvious morphology. Optical colonoscopies, while highly effective, rely on direct visualization to detect changes on the surface mucosa that are consistent with dysplasia. Recent advances in endoscopy techniques and molecular imaging permit microscale visualization of the colonic mucosa. These technologies can be combined with various molecular probes that recognize and target heterogenous lesion surfaces to achieve early, real-time, and potentially non-invasive, detection of pre-cancerous lesions. The primary goal of this review is to contextualize existing and emergent CRC surface biomarkers and assess each’s potential as a candidate marker for early marker-based detection of CRC lesions. CRC markers that we include were stratified by the level of support gleaned from peer-reviewed publications, abstracts, and databases of both CRC and other cancers. The selected biomarkers, accessible on the cell surface and preferably on the luminal surface of the colon tissue, are organized into three categories: (1) established biomarkers (those with considerable data and high confidence), (2) emerging biomarkers (those with increasing research interest but with less supporting data), and (3) novel candidates (those with very recent data, and/or supportive evidence from other tissue systems). We also present an overview of recent advances in imaging techniques useful for visual detection of surface biomarkers, and discuss the ease with which these methods can be combined with microscopic visualization.

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“…EphB4 is pathologically overexpressed in various malignant tumors, including breast cancer [33][34][35], lung cancer [36][37][38], gastric cancer [39], colorectal cancer [40,41], acute myeloid leukemia [42], cervical cancer [43], glioma [44], ovarian cancer [45,46], prostate cancer [47,48], thyroid cancer [49,50], bladder cancer [51,52], and contributes to poor prognosis. Mutations in the phosphorylation site of the EphB4 intracellular region in lung cancer promote tumor growth in vitro [53].…”

Section: Introductionmentioning

confidence: 99%

A Sensitive Monoclonal Antibody B4Mab-7 against EphB4 Was Developed for Breast Cancers

Nanamiya¹,

Suzuki²,

Kaneko³

et al. 2023

Preprint

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The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest receptor tyrosine kinases family. EphB4 is essential for cell adhesion and motility during embryogenesis. Pathologically, EphB4 is overexpressed and contributes to poor prognosis in various tumors. Therefore, sensitive monoclonal antibodies (mAbs) should be developed to predict the prognosis for multiple tumors with high EphB4 expression, including breast and gastric cancers. This study aimed to develop highly sensitive and specific anti-EphB4 mAbs for several applications using the Cell-Based Immunization and Screening (CBIS) method. EphB4-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/EphB4) cells were immunized into mice, and we established an anti-EphB4 mAb (clone B4Mab-7), which is applicable for flow cytometry, western blotting, and immunohistochemistry. B4Mab-7 reacted with endogenous EphB4-positive breast cancer cell lines, MCF-7 and MDA-MB-468, but did not react with EphB4-knockout MCF-7 (BINDS-52) in flow cytometry. Dissociation constant (KD) values were determined to be 2.9 × 10‑9 M, 1.3 × 10‑9 M, and 3.3 × 10‑9 M by flow cytometric analysis for CHO/EphB4, MCF-7, and MDA-MB-468 cells, respectively. B4Mab-7 detected the EphB4 protein bands from breast cancer cells in western blotting, and stained breast cancer tissues immunohistochemistry. Altogether, B4Mab-7 demonstrated high sensitivity and specificity against EphB4 in various applications.

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Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery

Cited by 14 publications

References 28 publications

EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway

EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway

Beyond Colonoscopy: Exploring New Cell Surface Biomarkers for Detection of Early, Heterogenous Colorectal Lesions

A Sensitive Monoclonal Antibody B4Mab-7 against EphB4 Was Developed for Breast Cancers

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