Increased expression of bone morphogenetic protein‐7 in bone metastatic prostate cancer

Masuda, Hiroshi; Fukabori, Yoshitatsu; Nakano, Kenji; Takezawa, Yutaka; cSuzuki, Takanori; Yamanaka, Hidetoshi

doi:10.1002/pros.10193

Cited by 101 publications

(71 citation statements)

References 30 publications

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“…This protein has been highly conserved during evolution and it belongs to a novel family of BMP antagonists that includes the tumour suppressor DAN. The BMPs play a major role in bone formation and may facilitate bone metastases derived from prostate tumours (Masuda et al, 2003) as well as other cancers. DRM/Gremlin protein blocks the activity of BMP2, BMP4, and BMP7 with high affinity (Hsu et al, 1998;Merino et al, 1999) and possibly that of other growth factors in the TGFb superfamily.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers

et al. 2005

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The transforming growth factor b (TGFb)-signalling pathway is deregulated in many cancers. We examined the role of gene silencing via aberrant methylation of DRM/Gremlin and HPP1, which inhibit TGFb signalling, and RUNX3, which facilitates TGFb-signalling, of all genes that are thought to be tumour suppressors, are aberrantly expressed, and are thus thought to have important role in human cancers. We examined DRM/Gremlin mRNA expression in 44 cell lines and the promoter methylation status of DRM/Gremlin, HPP1, and RUNX3 in 44 cell lines and 511 primary tumours. The loss of DRM/Gremlin mRNA expression in human cancer cell lines is associated with DNA methylation, and treatment with the methylation inhibitor-reactivated mRNA expression (n ¼ 13). Methylation percentages of the three genes ranged from 0 -83% in adult tumours and 0 -50% in paediatric tumours. Methylation of DRM/Gremlin was more frequent in lung tumours in smokers, and methylation of all three genes was inversely correlated with prognosis in patients with bladder or prostate cancer. Our results provide strong evidence that these TGFb-related genes are frequently deregulated through aberrant methylation in many human malignancies.

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Section: Discussionmentioning

confidence: 99%

DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers

et al. 2005

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“…Cancer cell metastasis to distant organs is the major cause of death in almost all forms of cancer. Metastasis is a multi-step process, depends not only on rapid proliferation of tumour cells, but also on other biological behaviors including motility, invasiveness, and metastatic potential (28,29). Tumour invasion is a critical step in tumour metastasis, and the understanding of this process may lead to appropriate therapies for treating cancer.…”

Section: Discussionmentioning

confidence: 99%

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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“…However, available data on involvement of BMP family members in cancerogenesis is conflicting. BMP-7 inhibits growth of prostate cancer cells, and was strongly downregulated in malignant tissue compared to correspondent healthy prostatic tissue (29). Increased BMP-7 expression was found in various human cancers, including malignant melanoma, breast cancer, prostate cancer, ovarian cancer, osteosarcoma and colorectal cancer (12-18, 30, 31).…”

Section: Comparison Of Survivors and Deceased Patientsmentioning

confidence: 99%

Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma

Bašić‐Jukić¹,

Hudolin²,

Radic-Antolic³

et al. 2010

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2 ABSTRACTRecent studies demonstrated that the expression pattern of bone morphogenetic protein 7(BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC).Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by RT-PCR and protein expression was analyzed by immunohistochemistry.RT-PCR showed strong downregulation of BMP-7 mRNA in cancer tissue.

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Increased expression of bone morphogenetic protein‐7 in bone metastatic prostate cancer

Cited by 101 publications

References 30 publications

DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers

DNA methylation-associated inactivation of TGFβ-related genes DRM/Gremlin, RUNX3, and HPP1 in human cancers

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

Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma

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