The nuclear variant of bone morphogenetic protein 2 (nBMP2) is expressed in macrophages and alters calcium response

Freitas, Claudia M. Tellez; Burrell, Haley R.; Valdoz, Jonard Corpuz; Hamblin, Garrett J.; Raymond, Carlee M.; Cox, Tyler D.; Johnson, Deborah; Andersen, Joshua L.; Weber, K. Scott; Bridgewater, Laura C.

doi:10.1038/s41598-018-37329-5

Cited by 3 publications

(2 citation statements)

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“…Further, nBMP-2 is translated in the cytoplasm and translocated to the nucleus by means of an embedded bipartite nuclear localization signal. Freitas et al investigated the possible role of nBMP-2 macrophages isolated from naïve (uninfected) nBmp2NLS tm mutant mice, demonstrating that the impairment of nBMP-2 induces alteration in intracellular Ca 2+ transport [6]. This datum was in agreement with the evidence that the impairment of nBMP-2 leads to muscular, neurological, and immune phenotypes, all of which are consistent with aberrant intracellular calcium (Ca 2+ ) response in a mouse model.…”

Section: Introductionmentioning

confidence: 63%

“…Thus, it is possible that in breast cancer, BMPs, and in particular BMP-2, can be involved simultaneously in EMT, BOLCs origin, and the formation of microcalcifications. To further complicate matters, Tellez Freitas et al recently demonstrated that the nuclear variant of BMP-2 (nBMP2) is expressed in macrophages and can alter the calcium homeostasis [6]. Therefore, it is possible to hypothesize that the occurrence of these two events is due to the presence of the two variants of BMP-2.…”

Section: Discussionmentioning

confidence: 99%

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BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

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This study aims to investigate the possible different roles of the BMP-2 variants, cytoplasmic and nuclear variant, in both epithelial to mesenchymal transition and in microcalcifications origin in human breast cancers. To this end, the in situ expression of cytoplasmic and nuclear BMP-2 was associated with the expression of the main epithelial to mesenchymal transition biomarkers (e-cadherin and vimentin) and molecules involved in bone metabolisms (RUNX2, RANKL, SDF-1) by immunohistochemistry. In addition, the expression of cytoplasmic and nuclear BMP-2 was associated with the presence of microcalcifications. Our data showed a significant association among the number of cytoplasmic BMP-2-positive cells and the number of both vimentin (positive association) and e-cadherin (negative association) positive breast cells. Conversely, no associations were found concerning the nuclear BMP-2-positive breast cells. Surprisingly, the opposite result was obtained by analyzing the variants of BMP-2 and both the expression of RANKL and SDF-1 and the presence of microcalcifications. Specifically, the presence of microcalcifications was related to the expression of nuclear BMP-2 variant rather than the cytoplasmic one, as well as a strong association between the number of nuclear BMP-2 and the expression of the main breast osteoblast-like cells (BOLCs) biomarkers. To further corroborate these data, an in vitro experiment for demonstrating the co-expression of nBMP-2 and RANKL or vimentin or SDF-1 in breast cancer cells that acquire the capability to produce microcalcifications was developed. These investigations confirmed the association between the nBMP-2 expression and both RANKL and SDF-1. The data supports the idea that whilst cytoplasmic BMP-2 can be involved in epithelial to mesenchymal transition phenomenon, the nuclear variant is related to the essential mechanisms for the formation of breast microcalcifications. In conclusion, from these experimental and translational perspectives, the complexity of BMP-2 signaling will require a detailed understanding of the involvement of specific BMP-2 variants in breast cancers.

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Section: Introductionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

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Recent Progress in Emerging Novel MXenes Based Materials and their Fascinating Sensing Applications

Khan

Tareen

Iqbal

et al. 2023

Small

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Early transition metals based 2D carbides, nitrides and carbonitrides nanomaterials are known as MXenes, a novel and extensive new class of 2D materials family. Since the first accidently synthesis based discovery of Ti3C2 in 2011, more than 50 additional compositions have been experimentally reported, including at least eight distinct synthesis methods and also more than 100 stoichiometries are theoretically studied. Due to its distinctive surface chemistry, graphene like shape, metallic conductivity, high hydrophilicity, outstanding mechanical and thermal properties, redox capacity and affordable with mass‐produced nature, this diverse MXenes are of tremendous scientific and technological significance. In this review, first we'll come across the MXene based nanomaterials possible synthesis methods, their advantages, limitations and future suggestions, new chemistry related to their selected properties and potential sensing applications, which will help us to explain why this family is growing very fast as compared to other 2D families. Secondly, problems that help to further improve commercialization of the MXene nanomaterials based sensors are examined, and many advances in the commercializing of the MXene nanomaterials based sensors are proposed. At the end, we'll go through the current challenges, limitations and future suggestions.

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Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer

et al. 2022

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Introduction Breast microcalcifications is a characteristic feature in diagnostic imaging and a prognostic factor of breast cancer. However, the underlying mechanisms of breast microcalcifications formation are not fully understood. Previous studies have shown that upregulation of bone morphogenetic protein 2 (BMP-2) is associated with the occurrence of microcalcifications and tumor-associated macrophages (TAMs) in the tumor microenvironment can secrete BMP-2. The aim of this study is to elucidate the role of secretion of BMP-2 by TAMs in promoting microcalcifications of breast cancer through immunohistochemical staining and co-culturing of breast cancer cells with TAMs. Methods A total of 272 patients diagnosed with primary invasive breast cancer from January 2010 to January 2012 in the First Hospital of China Medical University were included in this study. Immunohistochemical staining of CD68 (marker of entire macrophages), CD168 (marker of the M2-like macrophages) and BMP-2 were performed on 4-μm tissue microarray (TMA) sections. Following induction, THP-1 cells were differentiated to M2-like TAMs and were then co-cultured with breast cancer cells (MCF-7). Calcifications and BMP-2 expression were analyzed by Alizarin Red S staining and western blot, respectively. Results Immunohistochemical analysis showed that the expression of CD168 was significantly increased in tissues with microcalcifications and was correlated with the expression of BMP-2 and poor prognosis. The formation of cellular microcalcifications and BMP-2 expression were significantly increased in MCF-7 cells co-cultured with TAMs compared with MCF-7 cells alone. Conclusions These findings support the hypothesis that TAMs secrete BMP-2 to induce microcalcifications in breast cancer cells and influence prognosis via multiple pathways including BMP-2 and its downstream factors.

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The nuclear variant of bone morphogenetic protein 2 (nBMP2) is expressed in macrophages and alters calcium response

Cited by 3 publications

References 57 publications

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Recent Progress in Emerging Novel MXenes Based Materials and their Fascinating Sensing Applications

Secretion of BMP-2 by tumor-associated macrophages (TAM) promotes microcalcifications in breast cancer

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