Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells

Yao, Xiaosai; Labelle, Myriam; Lamb, Carla; Dugan, John M.; Williamson, Christina; Spencer, Donna R.; Christ, Kimberly; Keating, Ryan O.; Lee, W. David; Paradis, G; Begum, Shahinoor; Hynes, Richard O.; Wittrup, K. Dane

doi:10.1002/ijc.28312

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Notably, a positive correlation between high CD24 expression and enhanced cell proliferation in vitro and in vivo was reported previously (6). For example, CD24 1 cells from pleural effusions of different carcinomas revealed increased tumorigenicity in immunodeficient mice (41). Further evidence for the impact of CD24 was previously provided by the comparison of CD24 low and CD24 high subpopulations of MCF-7 cells (42).…”

Section: Discussionsupporting

confidence: 52%

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Topotecan‐induced ABCG2 expression in MCF‐7 cells is associated with decreased CD24 and EpCAM expression and a loss of tumorigenicity

et al. 2015

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Human breast cancer shows a considerable heterogeneity regarding the expression of CD24, CD44, EpCAM, and HER2. These markers are involved in cell adhesion, migration, and proliferation, and thus affect metastasis and, in turn, patient's outcome. The ATP-driven efflux pump (ABC transporter) breast cancer resistance protein (BCRP, ABCG2) is known to confer resistance to a wide variety of structurally unrelated cytostatics and defines subpopulations with enhanced tumor-initiating capacity. The expression of ABCG2 can be induced by treatment with different cytostatic drugs. Concurrent effects of such treatments on the expression of the aforementioned marker proteins and cellular properties related to cancer-initiating cells have not been examined thoroughly. Here, we investigated the effect of the ABCG2 substrate topotecan on the MCF-7 breast cancer cell line and analyzed CD24, CD44, EpCAM, and HER2 expression by flow cytometry. Moreover, we examined the impact of topotecan treatment on the sphere-forming ability in vitro and the tumorigenicity in immunodeficient NMRInu/nu and NSG mice. We found an elevated ABCG2 expression in MCF-7 cells in the presence of 500 nM topotecan. Compared with untreated MCF-7 cells, the application of topotecan induced a subpopulation with decreased CD24/EpCAM expression, whereas CD44 expression remained largely unchanged. Topotecan-treated cells showed an impaired mammosphere formation capacity in vitro and reduced tumorigenicity in immunodeficient mice. The data indicate that ABCG2 induction is not necessarily linked to increased tumorigenicity and suggest a major role of CD24 and EpCAM for the preservation of self-renewal capacity in MCF-7 cells and tumor outgrowth in vivo. V C 2015 International Society for Advancement of Cytometry

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Section: Discussionsupporting

confidence: 52%

“…1 cells from pleural effusions of different carcinomas revealed increased tumorigenicity in immunodeficient mice (41). Further evidence for the impact of CD24 was previously provided by the comparison of CD24 low and CD24 high subpopulations of MCF-7 cells (42).…”

Section: Abcg2mentioning

confidence: 81%

Topotecan‐induced ABCG2 expression in MCF‐7 cells is associated with decreased CD24 and EpCAM expression and a loss of tumorigenicity

et al. 2015

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“…High levels of CD24 detected by immunohistochemistry had a significantly increased likelihood of disease progression and cancer‐related death for lung cancer patients (Kristiansen et al , ; Lee et al , ). Disseminated lung tumor cells from malignant pleural effusions also express CD24 (Yao et al , ). On the other hand, CD24‐negative/low membrane expression was significantly correlated with poor differentiation and worse survival in lung cancers (Damelin et al , ).…”

Section: Introductionmentioning

confidence: 99%

Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis

et al. 2014

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Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24-dependent and Yap/Taz-dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease.

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“…Thus, increasingly falsenegative results might correlate to EMT [92] . The detection of EpCAM-negative cells might be possible by using other surface markers, such as N-cadherin, EGFR or cancer stem cell markers, such as CD44 [89,93,94] . In colorectal carcinomas, plastin3 was identified as a potential target for cells undergoing EMT because its expression is not altered during this process [95] .…”

Section: A Discussion Of the Results From Studies On Head And Neck Camentioning

confidence: 99%

Squamous cell carcinoma of the oral cavity and circulating tumour cells

Wikner

Gröbe

Pantel

2014

WJCO

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Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma (OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells (CTCs) and disseminated tumour cells (DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool to determine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised. Core tip: Oral squamous cell carcinoma (OSCC), among head and neck cancer, is related to poor survival rates despite considerable advances in diagnosis and treatment. Therefore, detecting tumour cell dissemination early and understanding the underlying mechanisms are crucial for predicting prognosis, relapse and survival. According to previous findings, circulating tumour cells (CTCs) and disseminated tumour cells (DTCs) might serve as prognostic markers to supplement routine staging and support determining individual therapeutic interventions. This review focuses on summarising the current knowledge about the detection of CTCs/DTCs with special emphasis on patients suffering from OSCC. The translational relevance of CTCs/DTCs and challenges for clinical application are highlighted.Wikner J, Gröbe A, Pantel K, Riethdorf S. Squamous cell carcinoma of the oral cavity and circulating tumour cells.

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Determination of 35 cell surface antigen levels in malignant pleural effusions identifies CD24 as a marker of disseminated tumor cells

Cited by 14 publications

References 24 publications

Topotecan‐induced ABCG2 expression in MCF‐7 cells is associated with decreased CD24 and EpCAM expression and a loss of tumorigenicity

Topotecan‐induced ABCG2 expression in MCF‐7 cells is associated with decreased CD24 and EpCAM expression and a loss of tumorigenicity

Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis

Squamous cell carcinoma of the oral cavity and circulating tumour cells

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