Nature communications, 2019-09, Vol.10 (1), p.4404-14, Article 4404
2019
Details
- Autor(en) / Beteiligte
- Titel
- The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis
- Ist Teil von
- Nature communications, 2019-09, Vol.10 (1), p.4404-14, Article 4404
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Bone is one of the most common sites for metastasis across cancers. Cancer cells that travel through the vasculature and invade new tissues can remain in a non-proliferative dormant state for years before colonizing the metastatic site. Switching from dormancy to colonization is the rate-limiting step of bone metastasis. Here we develop an ex vivo co-culture method to grow cancer cells in mouse bones to assess cancer cell proliferation using healthy or cancer-primed bones. Profiling soluble factors from conditioned media identifies the chemokine CXCL5 as a candidate to induce metastatic colonization. Additional studies using CXCL5 recombinant protein suggest that CXCL5 is sufficient to promote breast cancer cell proliferation and colonization in bone, while inhibition of its receptor CXCR2 with an antagonist blocks proliferation of metastatic cancer cells. This study suggests that CXCL5 and CXCR2 inhibitors may have efficacy in treating metastatic bone tumors dependent on the CXCL5/CXCR2 axis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-12108-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_1bfdfe5013bb48ed8014130e01ca4ba9
- Format
- –
- Schlagworte
- Animals, Bone cancer, Bone Neoplasms - genetics, Bone Neoplasms - metabolism, Bone Neoplasms - secondary, Bone tumors, Bones, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Cell culture, Cell growth, Cell Line, Tumor, Cell Movement - drug effects, Cell Movement - genetics, Cell proliferation, Cell Proliferation - drug effects, Cell Proliferation - genetics, Chemokine CXCL5 - antagonists & inhibitors, Chemokine CXCL5 - genetics, Chemokine CXCL5 - metabolism, Chemokines, Colonization, Conditioning, CXCR2 protein, Dormancy, Epithelial-Mesenchymal Transition - drug effects, Epithelial-Mesenchymal Transition - genetics, Female, Humans, Metastases, Metastasis, Mice, Transgenic, Middle Aged, Phenylurea Compounds - pharmacology, Receptors, Interleukin-8B - antagonists & inhibitors, Receptors, Interleukin-8B - genetics, Receptors, Interleukin-8B - metabolism, Signal Transduction - drug effects, Signal Transduction - genetics, Tumors