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Query: UMLS:C0153690 (
bone metastases
)
6,382
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A case is reported of a man who experienced hypercalcemia as a result of developing liver and renal-cell cancer. Repeated skeletal surveys and bone scans failed to reveal any
bone metastases
. The hypercalcemia was unresponsive to hydration and oral phosphate. However, it responded immediately to oral administration of indomethacin. The mechanism of this calcium-lowering effect is unknown. On the death of the patient, biopsies of the metastic liver and lung tissue were performed. The liver metastatis yielded 7 times the
PGE
(prostaglandin E)-like and 5 times the PGF-like material found in the normal adjacent liver. The lung metastatis yielded only 1/2 the
PGE
-like and PGF-like material obtained from normal adjacent lung. The results of this case study would indicate that some forms of hypercalcemia secondary to neoplastic disease are responsive to indomethacin and may be due to increased PG production by the tumor tissue.
...
PMID:Indomethacin-responsive hypercalcemia in a patient with renal-cell adenocarcinoma. 483 87
Both Wnt signaling and prostaglandin E(2) (
PGE
(2)) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa)
bone metastases
. We investigated the effects of
PGE
(2) on Wnt signaling in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells. We demonstrate that low dose
PGE
(2) (0.1 microM) promotes Wnt signaling while higher doses of
PGE
(2) (1.0-10 microM) inhibit these same parameters in osteoblast-lineage cells. The differential effects of low vs high-dose
PGE
(2) on pre-osteoblasts may be attributed to dose-dependent modulation of prostaglandin receptor (EP) subtype expression; with lower doses increasing the expression the cAMP-stimulatory EP4 receptor subtype and higher doses increasing the expression of the cAMP-inhibitory EP3 receptor subtype. Moreover, we demonstrate that high expression levels of COX-2 and
PGE
(2) promote the secretion of Wnt inhibitors from prostate cancer cells. These data demonstrate that there are dose-dependent effects of
PGE
(2) on Wnt activation in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells which may have clinical implications in the management.
...
PMID:Prostaglandin E2 modulates components of the Wnt signaling system in bone and prostate cancer cells. 2022 93
Breast cancer is one of the most common and devastating malignancies among women worldwide. Recent evidence suggests that malignant progression is also driven by processes involving the sphingolipid molecule sphingosine 1-phosphate (S1P) and its binding to cognate receptor subtypes on the cell surface. To investigate the effect of this interaction on the metastatic phenotype, we used the breast cancer cell line MDA-MB-231 and the sublines 4175 and 1833 derived from lung and
bone metastases
in nude mice, respectively. In both metastatic cell lines expression of the S1P
3
receptor was strongly upregulated compared to the parental cells and correlated with higher S1P-induced intracellular calcium ([Ca
2+
]
i
), higher cyclooxygenase (COX)-2 and microsomal prostaglandin (PG) E
2
synthase expression, and consequently with increased
PGE
2
synthesis.
PGE
2
synthesis was decreased by antagonists and siRNA against S1P
3
and S1P
2
. Moreover, in parental MDA-MB-231 cells overexpression of S1P
3
by cDNA transfection also increased
PGE
2
synthesis, but only after treatment with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine, indicating reversible silencing of the COX-2 promoter. Functionally, the metastatic sublines showed enhanced migration and Matrigel invasion in adapted Boyden chamber assays, which further increased by S1P stimulation. This response was abrogated by either S1P
3
antagonism, COX-2 inhibition or
PGE
2
receptor 2 (EP
2
) and 4 (EP
4
) antagonism, but not by S1P
2
antagonism. Our data demonstrate that in breast cancer cells overexpression of S1P
3
and its activation by S1P has pro-inflammatory and pro-metastatic potential by inducing COX-2 expression and
PGE
2
signaling via EP
2
and EP
4
.
...
PMID:Upregulation of the S1P
3
receptor in metastatic breast cancer cells increases migration and invasion by induction of PGE
2
and EP
2
/EP
4
activation. 2761 30
Parathyroid hormone-related protein (PTHrP) expression in breast cancer is enriched in
bone metastases
compared to primary tumors. Human MCF7 breast cancer cells "home" to the bones of immune deficient mice following intracardiac inoculation, but do not grow well and stain negatively for Ki67, thus serving as a model of breast cancer dormancy
in vivo
. We have previously shown that PTHrP overexpression in MCF7 cells overcomes this dormant phenotype, causing them to grow as osteolytic deposits, and that PTHrP-overexpressing MCF7 cells showed significantly lower expression of genes associated with dormancy compared to vector controls. Since early work showed a lack of cyclic AMP (cAMP) response to parathyroid hormone (PTH) in MCF7 cells, and cAMP is activated by PTH/PTHrP receptor (PTHR1) signaling, we hypothesized that the effects of PTHrP on dormancy in MCF7 cells occur through non-canonical (i.e., PTHR1/cAMP-independent) signaling. The data presented here demonstrate the lack of cAMP response in MCF7 cells to full length PTHrP(1-141) and PTH(1-34) in a wide range of doses, while maintaining a response to three known activators of adenylyl cyclase: calcitonin, prostaglandin E
2
(
PGE
2
), and forskolin. PTHR1 mRNA was detectable in MCF7 cells and was found in eight other human breast and murine mammary carcinoma cell lines. Although PTHrP overexpression in MCF7 cells changed expression levels of many genes, RNAseq analysis revealed that PTHR1 was unaltered, and only 2/32 previous PTHR1/cAMP responsive genes were significantly upregulated. Instead, PTHrP overexpression in MCF7 cells resulted in significant enrichment of the calcium signaling pathway. We conclude that PTHR1 in MCF7 breast cancer cells is not functionally linked to activation of the cAMP pathway. Gene expression responses to PTHrP overexpression must, therefore, result from autocrine or intracrine actions of PTHrP independent of PTHR1, through signals emanating from other domains within the PTHrP molecule.
...
PMID:Parathyroid Hormone-Related Protein Negatively Regulates Tumor Cell Dormancy Genes in a PTHR1/Cyclic AMP-Independent Manner. 2986 73
