Bone morphogenetic proteins in breast cancer: dual role in tumourigenesis?

Alarmo, Emma Leena; Kallioniemi, Anne

doi:10.1677/erc-09-0273

Cited by 102 publications

(103 citation statements)

References 166 publications

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“…For example, in breast cancer, the information is truly limited. 32 We have previously shown that BMP4 is strongly expressed in breast cancer cell lines and primary breast tumors. 23,33 Furthermore, we proposed a bidirectional function for BMP4 as in vitro it reduced cancer cell proliferation and yet was able to simultaneously increase the migration and invasion of breast cancer cells.…”

mentioning

confidence: 97%

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Alarmo¹,

Huhtala

Korhonen

et al. 2013

Modern Pathology

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Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor b (TGFb) superfamily and are known to regulate cell proliferation, differentiation and motility, especially during development. BMP4 has an indispensable role in vertebrate development while limited information on BMP4 expression and function exists in adult tissues. Nevertheless, its contribution to cancer development and progression has gained increasing interest in recent years. Functional studies, especially in breast cancer, have implicated BMP4 both in inhibition of cell proliferation and in promotion of cell migration and invasion. To gain an insight into the function of BMP4 in normal and cancer tissues, BMP4 protein expression levels were analyzed by immunohistochemistry in 34 different normal organs/tissues, 34 different tumor types and finally in 486 breast cancer samples where possible associations between BMP4 and clinicopathological parameters were statistically evaluated. In over 20% of normal and malignant tissues, BMP4 was expressed at high level. Strong expression was observed particularly in some normal epithelial cells, such as bladder and stomach, and in squamous cell carcinomas. In breast cancer, strong BMP4 expression was detected in 25% of patients, and was associated with low proliferation index and increased frequency of tumor recurrence. Taken together, BMP4 is expressed in a subset of normal adult tissues and is likely to contribute to tissue homeostasis. However, in tumors, BMP4 expression levels vary considerably, implying diverse roles in different tumor types. This role is biphasic in breast cancer as BMP4 expression is linked to reduced proliferation and increased recurrence, thus corroborating our previous in-vitro functional data.

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mentioning

confidence: 97%

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Alarmo¹,

Huhtala

Korhonen

et al. 2013

Modern Pathology

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“…High levels of Thbs1 could inhibit tumor growth, while anti-sense inhibition of Thbs1 in certain tumors also inhibited growth [31]. Bmp family also played a dual role in tumorigenesis [32]. In addition, it has been investigated that Inhba and Inhbe were down-regulated in chemically induced hepatocarcinogenesis [33].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of malignant transformed rat hepatic stem-like cells by aflatoxin B1

Yang¹,

Ji²,

Chen³

et al. 2014

neo

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Exposure to aflatoxins is strongly associated with hepatocellular carcinoma (HCC). Hepatic progenitor cells have been suggested to participate in the development of HCC. To further explore the molecular basis of aflatoxin-induced carcinogenesis, we utilized transcriptome profiles to examine the global gene expression alterations of malignant transformed rat hepatic stem-like cells. WB-F344 cells were treated with continuous exposure to AFB1 (0.03, 0.1 and 0.2μM), and gained certain characteristics of transformed cells identified by soft agar assay. Microarray analyses of the transformed cells found that 785, 625, and 751 differentially expressed genes were detected in each exposure group, respectively. Hierarchical Clustering revealed that the effect of 0.1 and 0.2μM exposure on the cells was conformable. Importantly, Gene Ontology analysis showed that malignant transformation of the hepatic stem-like cells was closely correlated to biological process, related to cell motion, cell adhesion, immune response and signal transduction. Accordingly, biological pathways was focused mainly on focal adhesion, regulation of actin cytoskeleton, ECM-receptor interaction, MAPK, TGF-β and chemokine signaling pathway. A few genes involved in these pathways exhibited a dose response, including Cav2, Itgb3, Ccl2, Cx3cl1, Pdgfrb and Tmsb4x. These findings would contribute to a growing knowledgebase on the mechanism of aflatoxin-induced hepatocarcinogenesis.

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“…However, it is important to remember that BMPs can be either stimulatory or inhibitory in human cancer possibly dependent on the expression level and the microenvironment. 6 Gremlin binds and activates VEGFR2 efficiently, independent of complex formation with BMPs. In fact, the Gremlin/BMP complex is slightly more active on endothelial cells than Gremlin alone.…”

Section: Gremlin: Vexing Vegf Receptor Agonist ----------------------mentioning

confidence: 99%

“…7 On the other hand, the Gremlin/BMP complex fails to bind to and activate the BMP receptor. Therefore, potentially, Gremlin may not only neutralize negatively regulating BMPs in human cancer, 6 but also further enhance tumor growth by stimulating tumor angiogenesis (see figure). Gremlin may regulate tumor angiogenesis also indirectly, through induction of Angiopoietin-1.…”

Section: Gremlin: Vexing Vegf Receptor Agonist ----------------------mentioning

confidence: 99%

Gremlin: vexing VEGF receptor agonist

Claesson‐Welsh

2010

Blood

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Bone morphogenetic proteins in breast cancer: dual role in tumourigenesis?

Cited by 102 publications

References 166 publications

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Bone morphogenetic protein 4 expression in multiple normal and tumor tissues reveals its importance beyond development

Transcriptome profiling of malignant transformed rat hepatic stem-like cells by aflatoxin B1

Gremlin: vexing VEGF receptor agonist

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