Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment

Marina Brama, Sabrina Basciani, Sara Cherubini, Stefania Mariani, Silvia Migliaccio, Mario Arizzi, Giuseppe Rosano, Giovanni Spera, Lucio Gnessi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)61-72
Number of pages12
JournalEndocrine-Related Cancer
Volume14
Issue number1
DOIs
Publication statusPublished - Mar 2007

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Conditioned Culture Medium
Osteoblasts
Breast Neoplasms
Platelet-Derived Growth Factor Receptors
Bone Neoplasms
Estrogens
MCF-7 Cells
Receptor Protein-Tyrosine Kinases
Growth
Nude Mice
Estrogen Receptors
Protein-Tyrosine Kinases
Imatinib Mesylate
Phosphorylation
Neoplasm Metastasis
Bone and Bones
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Brama, M., Basciani, S., Cherubini, S., Mariani, S., Migliaccio, S., Arizzi, M., ... Gnessi, L. (2007). Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment. Endocrine-Related Cancer, 14(1), 61-72. https://doi.org/10.1677/erc.1.01307

Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment. / Brama, Marina; Basciani, Sabrina; Cherubini, Sara; Mariani, Stefania; Migliaccio, Silvia; Arizzi, Mario; Rosano, Giuseppe; Spera, Giovanni; Gnessi, Lucio.

In: Endocrine-Related Cancer, Vol. 14, No. 1, 03.2007, p. 61-72.

Research output: Contribution to journalArticle

Brama, M, Basciani, S, Cherubini, S, Mariani, S, Migliaccio, S, Arizzi, M, Rosano, G, Spera, G & Gnessi, L 2007, 'Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment', Endocrine-Related Cancer, vol. 14, no. 1, pp. 61-72. https://doi.org/10.1677/erc.1.01307
Brama, Marina ; Basciani, Sabrina ; Cherubini, Sara ; Mariani, Stefania ; Migliaccio, Silvia ; Arizzi, Mario ; Rosano, Giuseppe ; Spera, Giovanni ; Gnessi, Lucio. / Osteoblast-conditioned medium promotes proliferation and sensitizes breast cancer cells to imatinib treatment. In: Endocrine-Related Cancer. 2007 ; Vol. 14, No. 1. pp. 61-72.
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