Breast osteoblast-like cells: a new biomarker for the management of breast cancer

Scimeca, Manuel; Urbano, Nicoletta; Bonfiglio, Rita; Schillaci, Orazio; Bonanno, Elena

doi:10.1038/s41416-018-0255-y

Cited by 35 publications

(33 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RUNX2 is an essential transcription factor; during osteoblast differentiation, RUNX2 is weakly expressed in uncommitted mesenchymal cells, and its expression is upregulated in pre-osteoblasts, reaches the maximal level in immature osteoblasts, and is down-regulated in mature osteoblasts [27]. In breast cancer, the expression of RUNX2 has been related to both BOLCs [28] and cancer metastatization [29]. Considering this information, we are not surprised to note that the number of RUNX2-positive breast cells was associated with both variants of BMP-2.…”

Section: Discussionmentioning

confidence: 99%

“…This is a chemokine signaling molecule involved in osteoblast differentiation in both in-bone and extra-bone sites, where it can induce the formation of ectopic calcifications [31]. In breast cancer, the over-expression of SDF1 protein was associated with positive estrogen receptor (ER) status, the breast cancer subtype previously associated with the presence of BOLCs and the development of bone metastases [28,32]. The investigation concerning the microcalcifications, as well as the expression of RANKL and SDF-1, support the idea that nBMP-2 is involved in BOLCs differentiation and activities rather than EMT phenomenon.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the last years, numerous studies highlighted the role of breast microcalcifications in the pathophysiogenesis of both breast cancer occurrence and progression [3][4][5][6]15,16] . In particular, we recently demonstrated the presence of breast cancer cells with an osteoblast phenotype (breast osteoblast-like cells- BOLCs) able to product microcalcifications made of HA or MgHAp [7] .…”

Section: Discussionmentioning

confidence: 99%

“…In the last years, several studies investigated the cellular and molecular mechanisms involved in the breast cancer osteotropism [3][4][5][6] . In particular, our group described, for the first time, a new breast cancer cell type showing an osteoblast-like phenotype, the breast osteoblast-like cells (BOLCs) [7] .…”

Section: Introductionmentioning

confidence: 99%

Can microcalcifications' characteristics predict the risk of breast cancer metastasis to bone?

Bonfiglio¹,

Scimeca²,

Polidori³

et al. 2019

JCMT

Self Cite

View full text Add to dashboard Cite

Aim:To correlate the microcalcifications' characteristics, such as morphology and elemental compositions, with the occurrence of bone metastatic lesions at 5 years from diagnosis. Methods:In this retrospective study, we enrolled 70 patients from which we collected one breast biopsy each. From each biopsy, paraffin serial sections were obtained to perform histological classifications, immunohistochemical analyses and Energy Dispersive X-ray evaluation.Results: Microcalcifications analysis showed a significant association between the presence of calcium crystals made of magnesium substituted hydroxyapatite and the development of bone metastasis from 5 years from diagnosis. No significant association was observed by evaluation the morphological appearance of microcalcifications. Immunohistochemical analysis displayed a significant association between the expression of bone morphogenetic proteins 2 and pentraxin-3, two osteoblast induction factors, and the formation of bone metastatic lesions.Conclusion: Results here reported highlighted the possible use of breast microcalcifications as a negative prognostic marker of bone metastatic diseases. In particular, the association between elemental composition of breast microcalcifications and the formation of bone lesions can lay the foundation for the development of new in vivo diagnostic tools based on the analysis of microcalcifications and capable to predict the formation of bone metastasis.

show abstract

“…In this scenario, Scimeca et al reported a new vision about the possible involvement of breast osteoblast-like cells (BOLCs) in the carcinogenesis of lesions with a high propensity to form bone metastasis [8][9][10]. In one of these studies, the authors reported very preliminary data about the possible use of breast-specific gamma imaging (BSGI) with [ 99 mTc]Tc-Sestamibi for the detection of breast cancer lesions, characterized by the presence of BOLCs [8] and thus susceptible to bone metastasis. Despite these preliminary data, however, no diagnostic evaluation is currently available for early detection of breast cancer lesions expressing bone biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers

Urbano

Scimeca

Russo

et al. 2020

JCM

Self Cite

View full text Add to dashboard Cite

The main purpose of this pilot investigation was to evaluate the possible relationship among [99mTc]Tc-Sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of molecules involved in bone metabolism, such as estrogen receptor, bone morphogenetic proteins-2, and PTX3. To this end, forty consecutive breast cancer patients who underwent both breast-specific gamma imaging with [99mTc]Tc-Sestamibi and breast bioptic procedure were retrospectively enrolled. From each diagnostic paraffin block collected in the study, histological diagnosis, immunohistochemical investigations, and energy dispersive X-ray microanalysis were performed. Our data highlight the possible use of breast-specific gamma imaging with [99mTc]Tc-Sestamibi for the early detection of breast cancer lesions expressing bone biomarkers in the presence of breast osteoblast-like cells. Specifically, we show a linear association among sestamibi uptake, the presence of breast osteoblast-like cells, and the expression of estrogen receptor, bone morphogenetics proteins-2, and PTX3. Notably, we also observed an increase of [99mTc]Tc-Sestamibi in breast cancer lesions with magnesium-substituted hydroxyapatite. In conclusion, in this pilot study we evaluated data from the nuclear medicine unit and anatomic pathology department on breast cancer osteotropism, identifying a new possible interpretation of Breast Specific Gamma Imaging with [99mTc]Tc-Sestamibi analysis.

show abstract

Breast osteoblast-like cells: a new biomarker for the management of breast cancer

Cited by 35 publications

References 12 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

Can microcalcifications' characteristics predict the risk of breast cancer metastasis to bone?

Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers

Contact Info

Product

Resources

About