Osteoblasts modulate Ca2+ signaling in bone-metastatic prostate and breast cancer cells
| Autor: | Julia A. D'Ambrosio, Alessandro Fatatis |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Programmed cell death Cell signaling Time Factors Cell Survival Bone Neoplasms Breast Neoplasms Cell Communication Biology Metastasis Prostate cancer Mice Cancer stem cell Internal medicine Cell Line Tumor medicine Animals Humans Osteoblasts Prostatic Neoplasms Osteoblast General Medicine medicine.disease Coculture Techniques Endocrinology medicine.anatomical_structure Cell Transformation Neoplastic Oncology Cell culture Cancer cell Cancer research Calcium Signal Transduction |
| Zdroj: | Clinicalexperimental metastasis. 26(8) |
| ISSN: | 1573-7276 |
| Popis: | 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 (Ca(2+)) induced by agonist stimulation. This osteoblast promoted alteration of Ca(2+) signaling develops and reverts in a time-dependent manner. Most importantly, the Ca(2+) responses of cancer cells lacking bone metastatic potential are not affected by osteoblasts. The limited increase in cytosolic Ca(2+) observed in bone-metastatic cells does not result from depleted intracellular Ca(2+) stores but rather a decreased entry of Ca(2+) from the extracellular space. Interestingly, the inhibition of histone deacetylase in cancer cells replicates the changes in Ca(2+) signaling induced by osteoblasts, suggesting the participation of epigenetic mechanisms. Finally, cancer cells harvested from skeletal metastases induced in mice showed Ca(2+) responses identical to cells co-cultured with osteoblasts. However, Ca(2+) 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 Ca(2+), thereby facilitating their progression into macroscopic skeletal metastases. |
| Databáze: | OpenAIRE |
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