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Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment
- Source :
- Endocrine-related cancer. 14(1)
- Publication Year :
- 2007
-
Abstract
- Inhibition of platelet-derived growth factor receptor (PDGFR) signaling restricts the growth of human breast cancer in the bone of nude mice. We hypothesized that osteoblast-secreted substances may alter the response capacity of breast cancer cells to the PDGFRs tyrosine kinase inhibitor imatinib mesylate. We found that osteoblast-conditioned medium (OCM) increases the proliferation rate of the estrogen receptor negative (ER−) MDA-MB-231 and of the ER+ MCF-7 human breast cancer cell lines and the growth-promoting effect on ER+ cells is independent from estrogen. OCM significantly improved the dose- and the time-dependent sensitivity of the tumor cells to the anti-proliferative effect of imatinib. We also found that MDA-MB-231 and MCF-7 cells express the two PDGFRs subtypes, PDGFR-α and PDGFR-β, and OCM treatment increases the expression of the PDGFRs. Furthermore, imatinib inhibited the phosphorylation rate of its target tyrosine kinase receptors. We conclude that bone microenvironment, through osteoblast-secreted substances may cause estrogen-independent proliferation of breast cancer cells by a mechanism mediated by the induction of PDGFRs expression. The enhanced sensitivity of OCM-treated breast cancer cells to imatinib would justify investigation on the efficacy of imatinib in bone breast cancer metastasis.
- Subjects :
- Cancer Research
Receptor, Platelet-Derived Growth Factor alpha
medicine.drug_class
Endocrinology, Diabetes and Metabolism
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Receptor tyrosine kinase
Tyrosine-kinase inhibitor
Piperazines
Receptor, Platelet-Derived Growth Factor beta
Endocrinology
Growth factor receptor
Transforming Growth Factor beta
Cell Line, Tumor
medicine
Humans
RNA, Messenger
Phosphorylation
skin and connective tissue diseases
Cell Proliferation
Osteoblasts
biology
business.industry
Cancer
Imatinib
medicine.disease
Up-Regulation
Imatinib mesylate
Pyrimidines
Oncology
Receptors, Estrogen
Culture Media, Conditioned
Benzamides
Cancer research
biology.protein
Imatinib Mesylate
business
Tyrosine kinase
Platelet-derived growth factor receptor
medicine.drug
Subjects
Details
- ISSN :
- 13510088
- Volume :
- 14
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Endocrine-related cancer
- Accession number :
- edsair.doi.dedup.....b8f3457af99ca343fa4cc0fde4461832