Tumor endothelial marker 7 (TEM-7): A novel target for antiangiogenic therapy

Rouleau, Cecile; Weber, William; Mehraein, Khodadad; Smale, Robert; Curiel, Maritza; Callahan, Michelle; Roy, Amélie; Boutin, Paula; Martin, Thomas N.; Nacht, Mariana; Teicher, Beverly A.

doi:10.1016/j.mvr.2011.09.004

Cited by 20 publications

(24 citation statements)

References 38 publications

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“…Prior studies of TEM7 have shown more varied results. Expression in human tumor endothelium has been observed in a number of studies (22, 23, 48, 49). In mouse studies, however, TEM7 expression was demonstrated by RT-PCR in one study of human melanoma and liposarcoma xenografts (47) but not observed in syngeneic melanoma tumors or human colon cancer xenografts by in situ hybridization or by SAGE analysis (23, 46).…”

Section: Discussionmentioning

confidence: 96%

Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy

et al. 2014

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Circulating endothelial cells (CEC) are derived from multiple sources including bone marrow (circulating endothelial progenitors [CEP]) and established vasculature (mature CEC). Although CEC have shown promise as a biomarker for cancer patients, their utility has been limited in part by the lack of specificity for tumor vasculature and the different non-malignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor vs non-malignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTEC were present in esophageal cancer and non-small cell lung cancer (NSCLC) patients (N=40) and their levels decreased after surgical resection. These results demonstrate that CTEC are detectable in preclinical cancer models and cancer patients. Further, they suggest that CTEC offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity.

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Section: Discussionmentioning

confidence: 96%

Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy

et al. 2014

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“…PLXDC1 (previously known as tumor endothelial marker 7) is primarily associated with angiogenesis in the cancer field, including kidney cancers. 36 Recently, its increased expression in diabetic retinopathy has been reported. 37 We found that the MAGI2 expression correlates with renal function in glomeruli.…”

Section: Discussionmentioning

confidence: 99%

Functional Genomic Annotation of Genetic Risk Loci Highlights Inflammation and Epithelial Biology Networks in CKD

Ledó

Park

et al. 2015

Journal of the American Society of Nephrology

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Genome-wide association studies (GWASs) have identified multiple loci associated with the risk of CKD. Almost all risk variants are localized to the noncoding region of the genome; therefore, the role of these variants in CKD development is largely unknown. We hypothesized that polymorphisms alter transcription factor binding, thereby influencing the expression of nearby genes. Here, we examined the regulation of transcripts in the vicinity of CKD-associated polymorphisms in control and diseased human kidney samples and used systems biology approaches to identify potentially causal genes for prioritization. We interrogated the expression and regulation of 226 transcripts in the vicinity of 44 single nucleotide polymorphisms using RNA sequencing and gene expression arrays from 95 microdissected control and diseased tubule samples and 51 glomerular samples. Gene expression analysis from 41 tubule samples served for external validation. 92 transcripts in the tubule compartment and 34 transcripts in glomeruli showed statistically significant correlation with eGFR. Many novel genes, including ACSM2A/2B, FAM47E, and PLXDC1, were identified. We observed that the expression of multiple genes in the vicinity of any single CKD risk allele correlated with renal function, potentially indicating that genetic variants influence multiple transcripts. Network analysis of GFR-correlating transcripts highlighted two major clusters; a positive correlation with epithelial and vascular functions and an inverse correlation with inflammatory gene cluster. In summary, our functional genomics analysis highlighted novel genes and critical pathways associated with kidney function for future analysis.

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“…Consistent with these observations, significantly higher detection of TEM7 transcripts in colon carcinoma tissues than in the normal colon tissue (85% versus 21% of TEM7 ISH+, resp.) was identified using in situ hybridization techniques performed on frozen tissues [79]. Considering these results, the TEM7 is suggested to be an attractive and perspective prognostic marker in CRC patients.…”

Section: Tumor Endothelial Markers (Tems)mentioning

confidence: 99%

Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

Pietrzyk

2016

Disease Markers

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Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

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Tumor endothelial marker 7 (TEM-7): A novel target for antiangiogenic therapy

Cited by 20 publications

References 38 publications

Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy

Tumor Endothelial Markers Define Novel Subsets of Cancer-Specific Circulating Endothelial Cells Associated with Antitumor Efficacy

Functional Genomic Annotation of Genetic Risk Loci Highlights Inflammation and Epithelial Biology Networks in CKD

Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

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