The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis

Article

Abstract

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. Breast cancer cells often invade the bone tissue and remain dormant until they are induced to colonize the metastatic site. Here the authors develop an ex vivo co-culture system consisting of bone and cancer cells from mice and show that CXCL5 has a role in metastatic colonization in the bone.

Attributes

Attribute NameValues
Creator
  • Maria Cristina Miranda-Vergara

  • Shourik Dutta

  • Aishwarya Natarajan

  • Beth Facchine

  • Kristen Jackson

  • Lukas Nystrom

  • Jun Li

  • William Kaliney

  • Glen Niebur

  • Laurie Littlepage

Journal or Work Title
  • Nature Communications

Volume
  • 10

Issue
  • 1

Number of Pages
  • 14

ISSN
  • 20411723

ISBN
  • 4146701912108

Subject
  • IVIS Lumina

Publisher
  • Nature

Date Created
  • 2019-10-18

Language
  • English

Departments and Units
Record Visibility and Access Public
Content License
  • All rights reserved

Digital Object Identifier

doi:10.1038/s41467-019-12108-6

This DOI is the best way to cite this article.