Format

Send to

Choose Destination
PLoS One. 2017 Oct 2;12(10):e0185736. doi: 10.1371/journal.pone.0185736. eCollection 2017.

Breast cancer cell-derived fibroblast growth factors enhance osteoclast activity and contribute to the formation of metastatic lesions.

Author information

1
Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America.
2
Microbiology, Cancer Biology and Immunology Graduate Program, University of Minnesota, Minneapolis, Minnesota, United States of America.
3
Developmental and Surgical Science, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, United States of America.
4
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
5
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
6
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, United States of America.
7
Department of Diagnostic and Biological Science, School of Dentistry, University of Minnesota, Minneapolis, Minnesota, United States of America.
8
Center for Immunology, University of Minnesota, Minneapolis, Minnesota, United States of America.

Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) have been implicated in promoting breast cancer growth and progression. While the autocrine effects of FGFR activation in tumor cells have been extensively studied, little is known about the effects of tumor cell-derived FGFs on cells in the microenvironment. Because FGF signaling has been implicated in the regulation of bone formation and osteoclast differentiation, we hypothesized that tumor cell-derived FGFs are capable of modulating osteoclast function and contributing to growth of metastatic lesions in the bone. Initial studies examining FGFR expression during osteoclast differentiation revealed increased expression of FGFR1 in osteoclasts during differentiation. Therefore, studies were performed to determine whether tumor cell-derived FGFs are capable of promoting osteoclast differentiation and activity. Using both non-transformed and transformed cell lines, we demonstrate that breast cancer cells express a number of FGF ligands that are known to activate FGFR1. Furthermore our results demonstrate that inhibition of FGFR activity using the clinically relevant inhibitor BGJ398 leads to reduced osteoclast differentiation and activity in vitro. Treatment of mice injected with tumor cells into the femurs with BGJ398 leads to reduced osteoclast activity and bone destruction. Together, these studies demonstrate that tumor cell-derived FGFs enhance osteoclast function and contribute to the formation of metastatic lesions in breast cancer.

PMID:
28968431
PMCID:
PMC5624603
DOI:
10.1371/journal.pone.0185736
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center