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| Content Provider | Springer Nature Link |
|---|---|
| Author | D’Ambrosio, Julia Fatatis, Alessandro |
| Copyright Year | 2009 |
| Abstract | Metastatic prostate and breast cancers display a predilection for the skeleton. The high incidence of skeletal metastasis may be a reflection of favorable reciprocal interactions between the bone microenvironment and disseminated cancer cells. Here we show that bone-metastatic PC3-ML prostate cancer cells and MDA-231 breast cancer cells—when co-cultured with human osteoblasts—down-regulate the increase in cytosolic free calcium (Ca2+) induced by agonist stimulation. This osteoblast promoted alteration of Ca2+ signaling develops and reverts in a time-dependent manner. Most importantly, the Ca2+ responses of cancer cells lacking bone metastatic potential are not affected by osteoblasts. The limited increase in cytosolic Ca2+ observed in bone-metastatic cells does not result from depleted intracellular Ca2+ stores but rather a decreased entry of Ca2+ from the extracellular space. Interestingly, the inhibition of histone deacetylase in cancer cells replicates the changes in Ca2+ signaling induced by osteoblasts, suggesting the participation of epigenetic mechanisms. Finally, cancer cells harvested from skeletal metastases induced in mice showed Ca2+ responses identical to cells co-cultured with osteoblasts. However, Ca2+ signaling in cancer cells recovered from metastases to soft-tissues was not affected, emphasizing the role of the bone microenvironment in regulating the functional behavior of bone-metastatic cells. We propose that osteoblasts protect selected malignant phenotypes from cell death caused by an excessive increase in cytosolic Ca2+, thereby facilitating their progression into macroscopic skeletal metastases. |
| Starting Page | 955 |
| Ending Page | 964 |
| Page Count | 10 |
| File Format | |
| ISSN | 02620898 |
| Journal | Clinical & Experimental Metastasis |
| Volume Number | 26 |
| Issue Number | 8 |
| e-ISSN | 15737276 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2009-09-21 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Metastasis Bone microenvironment Osteoblast Calcium signaling Surgical Oncology Hematology Oncology Biomedicine general Cancer Research |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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