BMP7 influences proliferation, migration, and invasion of breast cancer cells

Alarmo, Emma-Leena; Pärssinen, Jenita; Ketolainen, Johanna; Savinainen, Kimmo; Karhu, Ritva; Kallioniemi, Anne

doi:10.1016/j.canlet.2008.09.028

Cited by 103 publications

(89 citation statements)

References 39 publications

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“…Buijs et al (18) showed that loss of BMP7 expression during prostate cancer progression could contribute to the acquisition of an invasive phenotype. Similar results have been reported in breast cancer cells (17). However, exogenous BMP7 increases cell migration and the invasion process.…”

Section: Discussionsupporting

confidence: 89%

“…The expression of BMP7 in particular correlates with tumour progression and disease recurrence. In mammary epithelial cell cancer (4,(15)(16)(17), BMP7 regulates the proliferation, migration, invasion and apoptosis, and has been associated with bone metastases, acting as a LIM domain-only 4 (LMO4) responsive gene. Furthermore, BMP7 inhibits estradiol-induced proliferation.…”

Section: Introductionmentioning

confidence: 99%

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Μolecular impact of bone morphogenetic proteinï¿½7, on lung cancer cells and its clinical significance

et al. 2012

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Abstract. The aim of this study was to investigate the expression of bone morphogenetic protein 7 (BMP7), in human pulmonary cancer tissues/cells and to evaluate the cellular impact of bone morphogenetic proteins on pulmonary cancer cells. BMP7 expression was determined in human lung cancer cell lines. The invasiveness and growth of cells transfected with BMP7, in vitro, were evaluated using the in vitro invasion assay and in vitro tumour models. Cellular migration was analysed using wounding assays. BMP7-positive tumours correlated with the absence of bone metastasis (P=0.040). In this analysis, we identified that 4 of 4 small cell lung cancer (SCLC) tissue specimens had no BMP7 expression, which illustrated that BMP7 may have no role in SCLC. BMP7 expression was not correlated with the overall survival time in lung cancer patients. Downregulation of BMP7 expression significantly inhibited the invasiveness of SPC-A1 cells (P<0.001) and forced-expression of BMP7 dramatically increased the motility of A549 cells. Overexpression of BMP7 in A549 cells and its knockdown in SPC-A1 cells did not significantly alter proliferation compared with the control cells (P>0.5 respectively). In conclusion, we have demonstrated that BMP7 has an important role in controlling lung cancer cell motility and invasiveness, without affecting the growth process, cell proliferation and cell apoptosis. A higher BMP7 expression may be an indicator for bone metastasis. The therapeutic role of BMP7 warrants further investigation. IntroductionLung cancer is one of the most fatal tumours worldwide. Distant metastasis is an important cause for the poor prognosis. Of the factors related to metastasis, bone morphogenetic proteins (BMPs) have been recently shown to regulate the aggressiveness of cancer cells (1-7). BMPs are multifunctional signaling molecules belonging to the transforming growth factor-β (TGF-β) superfamily, which play important roles in multiple cellular processes such as cell growth, differentiation, migration and apoptosis in various types of cancer (8-12). The Smad-dependent signaling pathway has been proven to be the canonical pathway for BMP function (13). In lung cancer, expression of the BMP family members has also been reported (1,14). For example, BMP2 protein could stimulate growth, migration and invasion of lung cancer cells, and is overexpressed in virtually all types of lung cancers, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Silencing of BMP3b expression during NSCLC development has been reported and the BMP3b promoter has been found to be methylated. Activation of the BMP4 signaling pathway negatively regulates the growth, and induces senescence of A549 lung adenocarcinoma cells. Thus, there may be a contrasting response to any given BMP, depending on the tumour and cell type. Despite the discordant results defining the specific effects of BMP7 in various types of cancer, published data underscore the important role that BMP7 plays in tumour development and metastasis. The expre...

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Μolecular impact of bone morphogenetic proteinï¿½7, on lung cancer cells and its clinical significance

et al. 2012

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“…To date, much reliance has been put on the osteo-inductive effect of BMPs (Garrison et al, 2007;Clokie and Sandor, 2008;Mesimaki et al, 2009). However, the cost, safety and effectiveness of growth factors have been the subject of controversy lately (Alarmo et al, 2009;Garrison et al, 2010;Zuk et al, 2011). Due to the several risks and disadvantages related to the use of growth factors, we studied OM as an alternative method to enhance osteogenic differentiation of hASCs.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic medium is superior to growth factors in differentiation of human adipose stem cells towards bone-forming cells in 3D culture

Tirkkonen¹,

Haimi²,

Huttunen³

et al. 2013

eCM

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Human adipose stem cells (hASCs) have been recently used to treat bone defects in clinical practice. Yet there is a need for more optimal scaffolds and cost-effective approaches to induce osteogenic differentiation of hASCs. Therefore, we compared the efficiency of bone morphogenetic proteins (BMP-2 and BMP-7), vascular endothelial growth factor (VEGF), and osteogenic medium (OM) for the osteoinduction of hASCs in 3D culture. In addition, growth factors were tested in combination with OM. Commercially available bioactive glass scaffolds (BioRestore) and biphasic calcium phosphate granules (BoneCeramic) were evaluated as prospective carriers for hASCs. Both biomaterials supported hASC-viability, but BioRestore resulted in higher cell number than BoneCeramic, whereas BoneCeramic supported more significant collagen production. The most efficient osteo-induction was achieved with plain OM, promoting higher alkaline phosphatase activity and collagen production than growth factors. In fact, treatment with BMP-2 or VEGF did not increase osteogenic differentiation or cell number significantly more than maintenance medium with either biomaterial. Moreover, BMP-7 treatment consistently inhibited proliferation and osteogenic differentiation of hASCs. Interestingly, there was no benefit from growth factors added to OM. This is the first study to demonstrate that OM enhances hASCdifferentiation towards bone-forming cells significantly more than growth factors in 3D culture.

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“…Prostate cancer tissues contain high levels of BMP-6 whereas its expression was found to be low in breast cancer tissues [27,47]. However, BMP-7 often inhibits proliferation and invasion of cells of many cancer types such as breast, prostate, kidney and lung cancers [54][55][56]. Moreover, xenograft study reveals the inhibition of osteolytic metastasis of breast cancer MDA-MB-231 cells in response to BMP-7 treatment [31].…”

Section: Bone Morphogenetic Proteins and Cancermentioning

confidence: 99%

An Update of Bone Morphogenetic Proteins as Biomarker and Therapy for Cancer

Rahman¹

2015

J Carcinog Mutagen

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BMP7 influences proliferation, migration, and invasion of breast cancer cells

Cited by 103 publications

References 39 publications

Μolecular impact of bone morphogenetic proteinï¿½7, on lung cancer cells and its clinical significance

Μolecular impact of bone morphogenetic proteinï¿½7, on lung cancer cells and its clinical significance

Osteogenic medium is superior to growth factors in differentiation of human adipose stem cells towards bone-forming cells in 3D culture

An Update of Bone Morphogenetic Proteins as Biomarker and Therapy for Cancer

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