期刊
MOLECULAR BIOLOGY OF THE CELL
卷 32, 期 10, 页码 1009-1019出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E19-12-0682
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资金
- Orthopaedic Research Society Collaborative Exchange Grant
- Harper Cancer Research Institute
- Walther Cancer Foundation Interdisciplinary Interface Training Program
- Advanced Diagnostics & Therapeutics Leiva Graduate Fellowship in Precision Medicine
- Walther Cancer Foundation
- Simon-Harper Inter-Institutional Research Team Grant
- Walther Cancer Foundation Engineering Novel Solutions
- Kelly Cares Foundation
- American Cancer Society Research Scholar Award
- NIH [R33 CA206922]
- S.A.S. Foundation for Cancer Research [HHS-0008-16SF]
- Indiana Clinical Translational Science Institute [NIH TL1 TR002531]
Metastatic breast cancer cells preferentially migrate toward trabecular bone, influenced by tissue culture environment, growth factors (such as leptin and interleukins), and the biomechanical properties of bone. Migration speed is not solely dependent on matrix stiffness, but also on chemotactic signals.
Metastasis is responsible for over 90% of cancer-related deaths, and bone is the most common site for breast cancer metastasis. Metastatic breast cancer cells home to trabecular bone, which contains hematopoietic and stromal lineage cells in the marrow. As such, it is crucial to understand whether bone or marrow cells enhance breast cancer cell migration toward the tissue. To this end, we quantified the migration of MDA-MB-231 cells toward human bone in two- and three-dimensional (3D) environments. First, we found that the cancer cells cultured on tissue culture plastic migrated toward intact trabecular bone explants at a higher rate than toward marrow-deficient bone or devitalized bone. Leptin was more abundant in conditioned media from the cocultures with intact explants, while higher levels of IL-1 beta, IL-6, and TNF alpha were detected in cultures with both intact bone and cancer cells. We further verified that the cancer cells migrated into bone marrow using a bioreactor culture system. Finally, we studied migration toward bone in 3D gelatin. Migration speed did not depend on stiffness of this homogeneous gel, but many more dendritic-shaped cancer cells oriented and migrated toward bone in stiffer gels than softer gels, suggesting a coupling between matrix mechanics and chemotactic signals.
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