The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation

Buijs, Jeroen T.; Horst, Geertje van der; Hoogen, Christel van den; Cheung, Hiu Wing; Rooij, Bert-Jan de; Kroon, Jan; Petersen, Maj; Overveld, Petra G.M. van; Pelger, Rob C.M.; Pluijm, Gabri van der

doi:10.1038/onc.2011.400

Cited by 115 publications

(99 citation statements)

References 52 publications

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“…In agreement with this, BMP7 expression has been shown to be inversely proportional to the tumourigenicity and invasive behaviour of MDA-MB-231 breast cancer cells. 17,18 However, expression of BMP7 in primary tumour biopsies appears to contradict this finding. In a clinical setting, the presence of high levels of BMP7 expression in primary tumours has been strongly associated with accelerated bone metastasis, especially from ductal carcinomas.…”

Section: Tumour Cell Invasion and Dissemination Into The Circulationcontrasting

confidence: 40%

Molecular alterations that drive breast cancer metastasis to bone

2015

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Epithelial cancers including breast and prostate commonly progress to form incurable bone metastases. For this to occur, cancer cells must adapt their phenotype and behaviour to enable detachment from the primary tumour, invasion into the vasculature, and homing to and subsequent colonisation of bone. It is widely accepted that the metastatic process is driven by the transformation of cancer cells from a sessile epithelial to a motile mesenchymal phenotype through epithelial-mesenchymal transition (EMT). Dissemination of these motile cells into the circulation provides the conduit for cells to metastasise to distant organs. However, accumulating evidence suggests that EMT is not sufficient for metastasis to occur and that specific tissue-homing factors are required for tumour cells to lodge and grow in bone. Once tumour cells are disseminated in the bone environment, they can revert into an epithelial phenotype through the reverse process of mesenchymal-epithelial transition (MET) and form secondary tumours. In this review, we describe the molecular alterations undertaken by breast cancer cells at each stage of the metastatic cascade and discuss how these changes facilitate bone metastasis.

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Section: Tumour Cell Invasion and Dissemination Into The Circulationcontrasting

confidence: 40%

Molecular alterations that drive breast cancer metastasis to bone

2015

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“…Moreover, BMP4 treatment resulted in inhibition of tumor growth and mortality in a glioblastoma mouse model (107). In addition, treatment with BMP2, BMP7, and particularly the heterodimeric BMP2/7 strongly reduced the size of the ALDH hi /CD44 hi /CD24 (À/low) breast cancer CSC subpopulation (108). In addition, pretreatment of breast cancer cells with BMPs for 72 hours before systemic inoculation of the cancer cells inhibited the formation of bone metastases (108).…”

Section: Implications For Therapymentioning

confidence: 99%

Epithelial Plasticity, Cancer Stem Cells, and the Tumor-Supportive Stroma in Bladder Carcinoma

Horst

Bos

Pluijm

2012

Molecular Cancer Research

142

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High recurrence rates and poor survival rates of metastatic bladder cancer emphasize the need for a drug that can prevent and/or treat bladder cancer progression and metastasis formation. Accumulating evidence suggests that cancer stem/progenitor cells are involved in tumor relapse and therapy resistance in urothelial carcinoma. These cells seem less affected by the antiproliferative therapies, as they are largely quiescent, have an increased DNA damage response, reside in difficult-to-reach, protective cancer stem cell niches and express ABC transporters that can efflux drugs from the cells. Recent studies have shown that epithelial-to-mesenchymal transition (EMT), a process in which sessile, epithelial cells switch to a motile, mesenchymal phenotype may render cancer cells with cancer stem cells properties and/or stimulate the expansion of this malignant cellular subpopulation. As cancer cells undergo EMT, invasiveness, drug resistance, angiogenesis, and metastatic ability seem to increase in parallel, thus giving rise to a more aggressive tumor type. Furthermore, the tumor microenvironment (tumor-associated stromal cells, extracellular matrix) plays a key role in tumorigenesis, tumor progression, and metastasis formation. Taken together, the secret for more effective cancer therapies might lie in developing and combining therapeutic strategies that also target cancer stem/progenitor cells and create an inhospitable microenvironment for highly malignant bladder cancer cells. This review will focus on the current concepts about the role of cancer stem cells, epithelial plasticity, and the supportive stroma in bladder carcinoma. The potential implications for the development of novel bladder cancer therapy will be discussed. Mol Cancer Res; 10(8); 995-1009. Ó2012 AACR. Bladder CancerWorldwide, an estimated number of 386,300 new cases and 150,200 deaths from bladder cancer occurred in 2008, with the majority of cases (77%) occurring in men. Thereby, bladder cancer is the seventh most common cancer and the ninth most common cause of cancer-related death in men. Bladder cancer is most common in developed countries, where 63% of the cases occurred in 2002. In Europe and the United States, for example, bladder cancer is the fourth most common cancer in males. Overall, the 5-year survival rate of bladder cancer is approximately 80%, and it varies with the stage of the tumor, ranging from 97% for carcinoma in situ to 6% for metastatic disease.Urothelial carcinoma is a heterogeneous disease and multifocal tumors can develop in the same patient. Multifocality can be explained by the monoclonal theory, that is, multiple tumors arise from a single transformed cell or by the field cancerization theory (1). In the latter, exposure of the urothelium to important risk factors for bladder cancer, such as occupational carcinogens induces changes at different sites of the urothelium. As described by Cheng and colleagues (1), urothelial carcinoma in situ is a well-established precursor of invasive bladder cancer and may be...

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“…Although autocrine TGF-b signals play important roles in maintaining the stem-cell-like properties and tumorigenic activity of glioma-initiating cells (GICs), BMP signals induce the differentiation of these cells (Piccirillo et al 2006;Lee et al 2008). BMPs also regulate the differentiation of other types of cancer stem cells, including colorectal and breast cancers (Lombardo et al 2011;Buijs et al 2012;Gao et al 2012;Zhang et al 2012). Taken together with their inhibitory effects on proliferation of various types of cancer cells, activation of BMP signals is expected to serve as a therapeutic strategy for cancer.…”

Section: Tumor Suppression By Bmp Signalsmentioning

confidence: 99%

Bone Morphogenetic Proteins

Katagiri¹,

Watabe²

2016

Cold Spring Harb Perspect Biol

402

355

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Bone morphogenetic proteins (BMPs), originally identified as osteoinductive components in extracts derived from bone, are now known to play important roles in a wide array of processes during formation and maintenance of various organs including bone, cartilage, muscle, kidney, and blood vessels. BMPs and the related "growth and differentiation factors" (GDFs) are members of the transforming growth factor b (TGF-b) family, and transduce their signals through type I and type II serine -threonine kinase receptors and their intracellular downstream effectors, including Smad proteins. Furthermore, BMP signals are finely tuned by various agonists and antagonists. Because deregulation of the BMP activity at multiple steps in signal transduction is linked to a wide variety of human diseases, therapeutic use of activators and inhibitors of BMP signaling will provide potential avenues for the treatment of the human disorders that are caused by hypo-and hyperactivation of BMP signals, respectively.

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The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation

Cited by 115 publications

References 52 publications

Molecular alterations that drive breast cancer metastasis to bone

Molecular alterations that drive breast cancer metastasis to bone

Epithelial Plasticity, Cancer Stem Cells, and the Tumor-Supportive Stroma in Bladder Carcinoma

Bone Morphogenetic Proteins

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