Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay

Baccelli, Irène; Schneeweiß, Andreas; Riethdorf, Sabine; Stenzinger, Albrecht; Schillert, Anja; Vogel, Vanessa; Klein, Corinna; Saini, Massimo; Bäuerle, Tobias; Wallwiener, Markus; Holland‐Letz, Tim; Höfner, Thomas; Sprick, Martin R.; Scharpff, Martina; Marmé, Frederik; Sinn, Hans‐Peter; Pantel, Klaus; Weichert, Wilko; Trumpp, Andreas

doi:10.1038/nbt.2576

Cited by 929 publications

(901 citation statements)

References 42 publications

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“…A recent study found that among circulating tumor cells in the blood of women with metastatic breast cancer, the cells that were capable of initiating tumors when injected into mice expressed the cell surface proteins CD47, CD44, and MET (29). Remarkably, as in the case of CD47, the expression of CD44 and MET is induced by hypoxia in a HIFdependent manner (41,53).…”

Section: Discussionmentioning

confidence: 99%

“…The prophagocytic signal triggered by CRT-LRP ligation is counterbalanced by the antiphagocytic signal triggered by CD47-SIRPα ligation (28). Analysis of circulating tumor cells isolated from the blood of patients with breast cancer revealed that CD47 expression identified a subpopulation of cells with the capability to generate tumor xenografts in mice (29). Here, we report that CD47 expression is induced in a HIF-dependent manner when human breast cancer cells are exposed to hypoxia.…”

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confidence: 81%

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HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

Zhang

Xiang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

312

256

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Increased expression of CD47 has been reported to enable cancer cells to evade phagocytosis by macrophages and to promote the cancer stem cell phenotype, but the molecular mechanisms regulating CD47 expression have not been determined. Here we report that hypoxia-inducible factor 1 (HIF-1) directly activates transcription of the CD47 gene in hypoxic breast cancer cells. Knockdown of HIF activity or CD47 expression increased the phagocytosis of breast cancer cells by bone marrow-derived macrophages. CD47 expression was increased in mammosphere cultures, which are enriched for cancer stem cells, and CD47 deficiency led to cancer stem cell depletion. Analysis of datasets derived from thousands of patients with breast cancer revealed that CD47 expression was correlated with HIF target gene expression and with patient mortality. Thus, CD47 expression contributes to the lethal breast cancer phenotype that is mediated by HIF-1.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 81%

HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

Zhang

Xiang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

312

256

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“…Breast cancer circulating tumor cells (CTCs) expressing stem cell markers were capable of forming metastatic lesions in mice. The number of stem cell marker-expressing CTCs, but not bulk CTCs, correlated with disease progression and an overall worse prognosis (16). Stem cell signaling pathways have also been found in aggressive variants of nonepithelial cancers.…”

mentioning

confidence: 99%

A basal stem cell signature identifies aggressive prostate cancer phenotypes

Smith

Sokolov

Uzunangelov

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

174

172

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Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACSpurified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organconfined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells.RNA-seq | prostate cancer | stem cell signature | basal cell | neuroendocrine prostate cancer

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“…2). Moreover, although very few attempts have been made so far, CTCs could be cultured in vitro (Yu et al 2014, Cayrefourcq et al 2015 and used to derive patient-personalized xenograft models (Baccelli et al 2013, Khoo et al 2016 (Fig. 2) which can allow to screen novel, more efficient drugs selective for metastatic tumors rather than the primary lesion.…”

Section: Exosomes and Tumor Microenvironment In Acc Progressionmentioning

confidence: 99%

The next step: mechanisms driving adrenocortical carcinoma metastasis

Lalli

Luconi²

2018

Endocrine-Related Cancer

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Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.

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Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay

Cited by 929 publications

References 42 publications

HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells

A basal stem cell signature identifies aggressive prostate cancer phenotypes

The next step: mechanisms driving adrenocortical carcinoma metastasis

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