Molecular Basis of Metastasis

Chiang, Anne C.; Massagué, Joan

doi:10.1056/nejmra0805239

Cited by 933 publications

(741 citation statements)

References 67 publications

(76 reference statements)

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“…The incidence of breast cancer accounts for 7-8% of the total number of malignant tumors (25). Metastatic progression of breast cancer is a complex and clinically daunting process (26)(27)(28)(29). Breast cancer is both genetically and histopathologically heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Sun

et al. 2016

Oncology Reports

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Abstract. MicroRNA (miRNA) is a type of endogenous non-coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines. To study the functional significance of miR-124, we overexpressed miR-124 with miR-124 mimics and observed breast cancer cell proliferation, colony formation, migration, and invasion abilities by in vitro cell culture experiments. Target prediction algorithms and luciferase reporter gene assays were used to identify the target genes of miR-124. We also knocked down miR-124 targets using short hairpin RNA (shRNA) constructs, and observed associated breast cancer cell characteristics by in vitro cell culture experiments. We found that miR-124 expression significantly decreased in breast cancer tissues and cells compared to normal tissues and cells. In addition, cell proliferation, colony formation, migration, and invasion were decreased after overexpression of miR-124 in breast cancer cells. Furthermore, we used several algorithms to identify the snail family zinc finger 2 (SNAI2) as a potential target gene of miR-124. The protein expression level and luciferase activity of the 3'-untranslated region of SNAI2 were significantly decreased in breast cancer cells transfected with miR-124 mimics. Cell proliferation, colony formation, migration, and invasion were also decreased after knockdown of SNAI2 by shRNA. In conclusion, our data suggest that miR-124 expression is decreased in breast cancer and plays an important role as a tumor suppressor gene by targeting SNAI2. These findings may reveal novel perspectives for clinical treatments against breast cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Sun

et al. 2016

Oncology Reports

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“…All primary neoplasms are biologically heterogeneous, and the process of metastasis is highly selective [1][2][3]6 Therefore, an in vitro method that can rapidly isolate the precursor cells of metastasis is highly desirable. Here, we have shown that culturing a heterogeneous population of breast cancer cells on 0.9% agar selects for the metastasis-initiating population of the cells and that much of the gene expression analyses of these cells are consistent with those of breast cancer cells selected after successive in vivo cycling in an experimental model of brain metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…1 Metastases originate from a selected subpopulation of cells that reside in a biologically heterogeneous primary tumor. 2,3 Results from experimental 4 and clinical 5 examinations indicate that most metastases are clonal in origin and that the metastatic process is highly selective. 6 Studies have also shown profound differences between local and disseminated cancers, 7 suggesting that information on primary tumors alone may not be sufficient to determine optimal therapeutic interventions.…”

mentioning

confidence: 99%

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Guo

Fan

Zhang

et al. 2011

The American Journal of Pathology

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An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic po-The vast majority of cancer deaths result from progressive growth of metastases that are resistant to conventional therapies. 1 Metastases originate from a selected subpopulation of cells that reside in a biologically heterogeneous primary tumor. 2,3 Results from experimental 4 and clinical 5 examinations indicate that most metastases are clonal in origin and that the metastatic process is highly selective. 6 Studies have also shown profound differences between local and disseminated cancers, 7 suggesting that information on primary tumors alone may not be sufficient to determine optimal therapeutic interventions. For this reason, researchers have directed considerable effort toward improving understanding of the molecular phenotypes of metastasis-initiating tumor cells.One widely used experimental approach to isolate populations of tumor cells with enhanced metastatic potential is an in vivo selection process in which tumor cells are implanted into syngeneic or immunodeficient mice and metastasis is allowed to occur. Tumor cells from the resultant metastatic lesions can be isolated and expanded to establish cell sublines, some of which may have higher metastatic capacity than the parental tumorcell population. 8 Comparative gene expression profiling of parental tumor cells and their metastatic subpopulations has yielded invaluable information regarding the genetic determinants critical for organ-specific metastasis. 9 For example, Kang et al 10 compared the transcriptional profiles of parental MDA-231 human breast cancer cells with those of a bone-colonizing variant of this cell line and reported the underlying gene expression signature required for organ tropism to bone. Investigators used a similar approach to identify genes whose expression is critical for metastasis of breast cancer cells to the brain 11 and lungs. 12 Nevertheless, although this in vivo selection technique has provided new insight into the cellular and molecular mechanisms that control site-specific metastasis, there are some disadvantages. Perhaps the principal drawback of in vivo selection is that it can be time-consuming,

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“…Despite recent advances, treatment of advanced breast cancer remains palliative, and the survival times for the patients vary greatly. Breast cancer displays a distinct metastatic pattern with the skeleton as predominant metastatic site [2,3]. About 65e75% of the patients with metastatic breast cancer develop bone metastases [4,5].…”

Section: Introductionmentioning

confidence: 99%

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

Schröder¹,

Fietz²,

Köhler

et al. 2017

European Journal of Cancer

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A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany. This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n Z 976) received BTA therapy. In 2014e2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6e70.8), 38 months (95% CI 29.4e44.2) to 28 months (95% CI 24.2 e31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.

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Molecular Basis of Metastasis

Cited by 933 publications

References 67 publications

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

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