Differential CD146 Expression on Circulating Versus Tissue Endothelial Cells in Rectal Cancer Patients: Implications for Circulating Endothelial and Progenitor Cells As Biomarkers for Antiangiogenic Therapy

Duda, Dan G.; Cohen, Kenneth S.; Tomaso, Emmanuelle di; Au, Patrick; Klein, Rachael J.; Scadden, David T.; Willett, Christopher G.; Jain, Rakesh K.

doi:10.1200/jco.2005.04.2861

Cited by 117 publications

(89 citation statements)

References 26 publications

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“…CD146 expression can be modulated within the tumor microenvironment. A recent study reported that CD146 expression varied in circulating endothelial cells with increased or different tumor burdens (11). Our study has also shown that CD146 is an inducible molecule on the stimulated endothelial cells using conditioned medium from hepatocarcinoma SMMC 7721, named SMMC 7721-CM.…”

Section: Introductionsupporting

confidence: 70%

Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-κB activation

Gao

Zhuang

et al. 2006

Molecular Cancer Therapeutics

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Our previous study showed that an anti-CD146 monoclonal antibody (mAb), AA98, which was raised against the vascular endothelial cells stimulated by a conditioned medium from hepatocarcinoma SMMC 7721 cells (SMMC 7721-CM), inhibited cell migration, angiogenesis, and tumor growth. However, the underlying mechanism was not elucidated. The objective of this study was to understand the mechanism by which mAb AA98 inhibits the endothelial cell migration and angiogenesis that is induced by SMMC 7721-CM. Using confocal imaging and biochemical studies, we found that SMMC 7721-CM induced nuclear factor KB (NF-KB) activation through the upstream p38 mitogen-activated protein kinase pathway, leading to the up-regulation of matrix metalloproteinase 9 and intercellular adhesion molecule 1 expression. Interestingly, all these activities stimulated by SMMC 7721-CM could be effectively inhibited by mAb AA98 in a dose-and time-dependent manner. Our data showed that the engagement of mAb AA98 with membrane protein CD146 inhibited p38 mitogen-activated protein kinase phosphorylation, suppressed NF-KB activation, and downregulated matrix metalloproteinase 9 and intercellular adhesion molecule 1 expression, suggesting that the suppression of NF-KB is a critical point for the inhibitory function of mAb AA98 on endothelial cell migration, angiogenesis, and tumor metastasis. These results will provide clues for a better understanding of the mechanisms underlying tumor angiogenesis as well as antiangiogenesis therapy.

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Section: Introductionsupporting

confidence: 70%

Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-κB activation

Gao

Zhuang

et al. 2006

Molecular Cancer Therapeutics

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“…Although this is a generally accepted CEC immunophenotype, reports are currently not available in which the endothelial origin of cells enumerated by those assays has been demonstrated unambiguously (Duda et al, 2006;Mancuso et al, 2006). As a result, studies on CEC that are in our opinion reliable, are scarce: only three studies are currently available, all based on CD146 driven magnetic isolation of CEC (Beerepoot et al, 2004;Woywodt et al, 2006;Rowand et al, 2007).…”

Section: Clinical Resultsmentioning

confidence: 99%

Circulating endothelial cells in oncology: pitfalls and promises

et al. 2008

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Adequate blood supply is a prerequisite in the pathogenesis of solid malignancies. As a result, depriving a tumour from its oxygen and nutrients, either by preventing the formation of new vessels, or by disrupting vessels already present in the tumour, appears to be an effective treatment modality in oncology. Given the mechanism by which these agents exert their anti-tumour activity together with the crucial role of tumour vasculature in the pathogenesis of tumours, there is a great need for markers properly reflecting its impact. Circulating endothelial cells (CEC), which are thought to derive from damaged vasculature, may be such a marker. Appropriate enumeration of these cells appears to be a technical challenge. Nevertheless, first studies using validated CEC assays have shown that CEC numbers in patients with advanced malignancies are elevated compared to healthy controls making CEC a potential tool for among other establishing prognosis and therapy-induced effects. In this review, we will address the possible clinical applications of CEC detection in oncology, as well as the pitfalls encountered in this process.

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“…Circulating endothelial cells are a very rare cell population, normally defined as mature endothelial cells shed from the vasculature and are considered to be a useful biomarker of vascular damage (Willett et al, 2004;Duda et al, 2006;Batchelor et al, 2007;Norden-Zfoni et al, 2007). In addition, the possibility to monitor circulating endothelial progenitor cells (CEPs) has been proposed as an attractive biomarker for anti-angiogenic agents after the seminal identification of circulating progenitors, which could grow out to highly proliferative endothelial outgrowth cells (EOCs) (Ingram et al, 2005;Shaked et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

et al. 2009

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Background: Blood-based biomarkers may be particularly useful for patient selection and prediction of treatment response for angiogenesis inhibitors. Circulating endothelial cells (CECs) and haematopoietic progenitor cells (HPCs) might have a role in tumour angiogenesis and in tumour growth. Measurement of CECs and HPCs in the blood of patients could be a simple, non-invasive way to monitor or predict responses to treatment. Methods: (VEGFR2 + ) CECs , (CD133 + ) HPCs, plasma vascular endothelial growth factor (VEGF) and erythropoietin were measured in blood from 25 non-small cell lung cancer (NSCLC) patients before and during treatment with sorafenib plus erlotinib (SO/ER). In order to assess the drug specificity of changes in CECs and HPCs, 18 patients treated with bevacizumab plus erlotinib (BV/ER) and 10 patients with erlotinib (ER) monotherapy were studied. Response was measured in all patient groups by Response Evaluation Criteria in Solid Tumors (RECIST). Results: At day 7, SO/ER-treated patients showed a three-fold increase in CECs ( P <0.0001) comparable to BV/ER-treated patients ( P <0.01), and the CECs did not change with erlotinib treatment ( P =0.8). At day 7, CD133 + /HPCs decreased with SO/ER treatment ( P <0.0001). HPC numbers did not change with either BV/ER or erlotinib. In SO/ER-treated patients pre-treatment CD133 + /HPCs were significantly lower in responders ( P =0.01) and pre-treatment CD133 + /HPC numbers lower than the median correlated with a longer time-to-progression (TTP) ( P =0.037). Conclusion: Pre-treatment CD133 + /HPCs are a promising candidate biomarker to further explore for use in selecting NSCLC patients who might benefit from SO/ER treatment.

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Differential CD146 Expression on Circulating Versus Tissue Endothelial Cells in Rectal Cancer Patients: Implications for Circulating Endothelial and Progenitor Cells As Biomarkers for Antiangiogenic Therapy

Cited by 117 publications

References 26 publications

Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-κB activation

Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-κB activation

Circulating endothelial cells in oncology: pitfalls and promises

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

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