Link between estrogen deficiency osteoporosis and susceptibility to bone metastases: A way towards precision medicine in cancer patients

Salamanna, Francesca; Borsari, Veronica; Contartese, Deyanira; Aldini, N. Nicoli; Fini, Milena

doi:10.1016/j.breast.2018.06.013

Cited by 19 publications

(15 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since estrogen deficiency is one of the main causes of menopausal osteoporosis (48), it would be interesting to explore whether the mechanism of 4HR action is also associated with estrogen levels in vivo, including increased estrogen receptor activity. However, since there is currently no evidence of a direct connection, future studies should investigate this potential relationship (47).The present study on osteoclastogenesis were consistent with those reported by Choi et al (23), which showed that 4HR improved OB function in ovariectomized rats, confirming the potential use of 4HR for the treatment of osteoporosis. A limitation of the present study was that it remains unclear if OBs also participated in the role of 4HR in this OVX model.…”

Section: Discussionsupporting

confidence: 91%

“…OVX is a procedure that results in decreased estrogen that has been valuable for osteoporosis research (39). The main characteristic of this model is the increased OC number and activity (47). In the present study, administration of 4HR in mice resulted in a significantly reduced degree of bone loss induced by OVX as evidenced by microCT and histology data.…”

Section: Discussionsupporting

confidence: 55%

See 1 more Smart Citation

4‑Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF‑κB signaling pathway and reverses bone loss in ovariectomized mice

Liu

Gao

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

4-Hexylresorcinol (4HR) is a small organic compound that is widely used as an antiseptic and antioxidant. In the present study, its role in osteoclastogenesis was investigated. Bone marrow-derived macrophages from mice were used to examine the role of 4HR in osteogenesis. An ovariectomy (OVX) mouse model was constructed to examine the effect of 4HR in vivo, followed by hematoxylin and eosin and tartrate resistant acid phosphatase staining. In the present study, 4HR effectively suppressed receptor activator of NF-κB ligand-induced osteoclastogenesis in a dose-dependent manner. 4HR was also found to significantly suppress the expression of osteoclast (OC)-specific markers, including tartrate-resistant acid phosphatase, cathepsin K, nuclear factor of activated T-cell cytoplasmic 1 and c-Fos in the presence of RANKL in BMMs. Furthermore, 4HR inhibited osteoclastogenesis by inhibiting the activation of the NF-κB signaling pathway in BMMs. Consistent with the in vitro results, 4HR effectively ameliorated OVX-induced bone loss and markedly reduced OC number in the proximal tibia in vivo. In conclusion, the present results suggested that 4HR inhibited osteoclastogenesis in vitro and rescued bone loss in vivo, suggesting that 4HR may serve as a novel therapeutic agent for osteoporosis treatment.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 55%

4‑Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF‑κB signaling pathway and reverses bone loss in ovariectomized mice

Liu

Gao

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…The inhibition of the intratibial Py8119 tumor growth observed in OVX Δ130-136 could likely be attributed to the unfavorable microenvironment induced by the damage from accumulative oxidative stress. In agreement, the increased tumor growth observed in OVX treated WT and R76W mice could be caused by increased bone resorption because of OVX-induced estrogen deficiency [ 33 , 34 ] but is unlikely to be caused by elevated oxidative stress, because we did not detect increased oxidative stress levels in the tibia of these animal models. Consistent with our in vitro results, a high oxidative stress level has an inhibitory effect on tumor growth.…”

Section: Discussionsupporting

confidence: 83%

Osteocytic Connexin Hemichannels Modulate Oxidative Bone Microenvironment and Breast Cancer Growth

Tian

Riquelme

et al. 2021

Cancers

View full text Add to dashboard Cite

Osteocytes, the most abundant bone cell types embedded in the mineral matrix, express connexin 43 (Cx43) hemichannels that play important roles in bone remodeling and osteocyte survival. Estrogen deficiency decreases osteocytic Cx43 hemichannel activity and causes a loss in osteocytes’ resistance to oxidative stress (OS). In this study, we showed that OS reduced the growth of both human (MDA-MB-231) and murine (Py8119) breast cancer cells. However, co-culturing these cells with osteocytes reduced the inhibitory effect of OS on breast cancer cells, and this effect was ablated by the inhibition of Cx43 hemichannels. Py8119 cells were intratibially implanted in the bone marrow of ovariectomized (OVX) mice to determine the role of osteocytic Cx43 hemichannels in breast cancer bone metastasis in response to OS. Two transgenic mice overexpressing dominant-negative Cx43 mutants, R76W and Δ130-136, were adopted for this study; the former inhibits gap junctions while the latter inhibits gap junctions and hemichannels. Under normal conditions, Δ130-136 mice had significantly more tumor growth in bone than that in WT and R76W mice. OVX increased tumor growth in R76W but had no significant effect on WT mice. In contrast, OVX reduced tumor growth in Δ130-136 mice. To confirm the role of OS, WT and Δ130-136 mice were administered the antioxidant N-acetyl cysteine (NAC). NAC increased tumor burden and growth in Δ130-136 mice but not in WT mice. Together, the data suggest that osteocytes and Cx43 hemichannels play pivotal roles in modulating the oxidative microenvironment and breast cancer growth in the bone.

show abstract

“…Recent advances in human-derived 3D cultures for studies on bone metastasis were nicely presented by Milena Fini from IRCCS Istituto Ortopedico Rizzoli, Bologna, (Italy). She explained the complexity of the interaction between tumor cells that metastasize in the bone inducing destructive osteolytic and/or bone forming osteoblastic lesions and the alteration of bone microenvironment producing factors that stimulate tumor growth [43]. When bone metastases were initially studied, one of the limitations was the complex nature of the bone environment.…”

Section: Session 4 3d-organoids Models As New Tools For Biomedical Rmentioning

confidence: 99%

Cell communication and signaling: how to turn bad language into positive one

Chiodoni

Martino

Zazzeroni

et al. 2019

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Cell-to-cell communication has a critical role during tumor development and progression, allowing cancer cell to reprogram not only the surrounding tumor microenvironment, but also cells located at distant sites. The crosstalk between neoplastic cells and accessory elements, such as immune and stromal cells, fosters several processes that are necessary for tumor progression and dissemination, such as angiogenesis, immune-escape, epithelial-tomesenchymal transition, invasion and multi-drug resistance. There are several means by which cells communicate to each other, either by direct cell interactions through membrane receptors and ligands, or by releasing soluble molecules, such as growth factors, cytokines and chemokines. More recently, additional means of cell communication have been identified, such as microRNAs and extracellular vesicles. These two peculiar ways of cellto-cell interaction were the focus of the 31st Annual Conference of the Italian Association of Cell Cultures (AICC).

show abstract

Link between estrogen deficiency osteoporosis and susceptibility to bone metastases: A way towards precision medicine in cancer patients

Cited by 19 publications

References 87 publications

4‑Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF‑κB signaling pathway and reverses bone loss in ovariectomized mice

4‑Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF‑κB signaling pathway and reverses bone loss in ovariectomized mice

Osteocytic Connexin Hemichannels Modulate Oxidative Bone Microenvironment and Breast Cancer Growth

Cell communication and signaling: how to turn bad language into positive one

Contact Info

Product

Resources

About