Dataset Information

The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis.

ABSTRACT: Recent data from the AZURE, ABCSG-12, and ZO-FAST clinical trials have challenged our understanding of the potential anticancer activity of zoledronic acid (ZOL). Although the results of these studies may appear to be conflicting on the surface, a deeper look into commonalities among the patient populations suggest that some host factors (i.e. patient age and endocrine status) may contribute to the anticancer activity of ZOL. Indeed, data from these large clinical trials suggest that the potential anticancer activity of ZOL may be most robust in a low-estrogen environment. However, this may be only part of the story and many questions remain to be answered to fully explain the phenomenon. Does estrogen override the anticancer activity of ZOL seen in postmenopausal women? Are hormones other than estrogen involved that contribute to this effect? Does the role of bone turnover in breast cancer (BC) growth and progression differ in the presence of various estrogen levels? Here, we present a review of the multitude of factors affected by different endocrine environments in women with BC that may influence the potential anticancer activity of ZOL.

SUBMITTER: Hadji P

PROVIDER: S-EPMC3477882 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis.

Hadji P P Coleman R R Gnant M M Green J J

Annals of oncology : official journal of the European Society for Medical Oncology 20120622 11

Recent data from the AZURE, ABCSG-12, and ZO-FAST clinical trials have challenged our understanding of the potential anticancer activity of zoledronic acid (ZOL). Although the results of these studies may appear to be conflicting on the surface, a deeper look into commonalities among the patient populations suggest that some host factors (i.e. patient age and endocrine status) may contribute to the anticancer activity of ZOL. Indeed, data from these large clinical trials suggest that the potenti ...[more]

PMID: 22730099

Similar Datasets

Project description:Extracellular ATP has been shown to either inhibit or promote cancer growth and migration; however, the mechanism underlying this discrepancy remained elusive. Here we demonstrate the divergent roles of ATP and adenosine released by bone osteocytes on breast cancers. We showed that conditioned media (CM) collected from osteocytes treated with alendronate (AD), a bisphosphonate drug, inhibited the migration of human breast cancer MDA-MB-231 cells. Removal of the extracellular ATP by apyrase in CM abolished this effect, suggesting the involvement of ATP. ATP exerted its inhibitory effect through the activation of purinergic P2X receptor signaling in breast cancer cells evidenced by the attenuation of the inhibition by an antagonist, oxidized ATP, as well as knocking down P2X7 with small interfering RNA (siRNA), and the inhibition of migration by an agonist, BzATP. Intriguingly, ATP had a biphasic effect on breast cancer cells-lower dosage inhibited but higher dosage promoted its migration. The stimulatory effect on migration was blocked by an adenosine receptor antagonist, MRS1754, ARL67156, an ecto-ATPase inhibitor, and A2A receptor siRNA, suggesting that in contrast to ATP, adenosine, a metabolic product of ATP, promoted migration of breast cancer cells. Consistently, non-hydrolyzable ATP, ATPγS, only inhibited but did not promote cancer cell migration. ATP also had a similar inhibitory effect on the Py8119 mouse mammary carcinoma cells; however, adenosine had no effect owing to the absence of the A2A receptor. Consistently, ATPγS inhibited, whereas adenosine promoted anchorage-independent growth of MDA-MB-231 cells. Our in vivo xenograft study showed a significant delay of tumor growth with the treatment of ATPγS. Moreover, the extent of bone metastasis in a mouse intratibial model was significantly reduced with the treatment of ATPγS. Together, our results suggest the distinct roles of ATP and adenosine released by osteocytes and the activation of corresponding receptors P2X7 and A2A signaling on breast cancer cell growth, migration and bone metastasis.

Dataset Information

The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis.

Publications

The impact of menopause on bone, zoledronic acid, and implications for breast cancer growth and metastasis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets