Tumor-induced pressure in the bone microenvironment causes osteocytes to promote the growth of prostate cancer bone metastases
Cross-talk between tumor cells and their microenvironment is critical for malignant progression. Cross-talk mediators, including soluble factors and direct cell contact, have been identified, but roles for the interaction of physical forces between tumor cells and the bone microenvironment have not...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2015-06, Vol.75 (11), p.2151-2158 |
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| creator | Sottnik, Joseph L Dai, Jinlu Zhang, Honglai Campbell, Brittany Keller, Evan T |
| description | Cross-talk between tumor cells and their microenvironment is critical for malignant progression. Cross-talk mediators, including soluble factors and direct cell contact, have been identified, but roles for the interaction of physical forces between tumor cells and the bone microenvironment have not been described. Here, we report preclinical evidence that tumor-generated pressure acts to modify the bone microenvironment to promote the growth of prostate cancer bone metastases. Tumors growing in mouse tibiae increased intraosseous pressure. Application of pressure to osteocytes, the main mechanotransducing cells in bone, induced prostate cancer growth and invasion. Mechanistic investigations revealed that this process was mediated in part by upregulation of CCL5 and matrix metalloproteinases in osteocytes. Our results defined the critical contribution of physical forces to tumor cell growth in the tumor microenvironment, and they identified osteocytes as a critical mediator in the bone metastatic niche. |
| doi_str_mv | 10.1158/0008-5472.CAN-14-2493 |
| format | Article |
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Cross-talk mediators, including soluble factors and direct cell contact, have been identified, but roles for the interaction of physical forces between tumor cells and the bone microenvironment have not been described. Here, we report preclinical evidence that tumor-generated pressure acts to modify the bone microenvironment to promote the growth of prostate cancer bone metastases. Tumors growing in mouse tibiae increased intraosseous pressure. Application of pressure to osteocytes, the main mechanotransducing cells in bone, induced prostate cancer growth and invasion. Mechanistic investigations revealed that this process was mediated in part by upregulation of CCL5 and matrix metalloproteinases in osteocytes. 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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Bone Neoplasms - pathology Bone Neoplasms - secondary Cell Proliferation - physiology Chemokine CCL5 - biosynthesis Gene Expression Regulation, Neoplastic Humans Male Matrix Metalloproteinases - biosynthesis Mice Neoplasm Metastasis Osteocytes - metabolism Osteocytes - pathology Pressure Prostatic Neoplasms - pathology Tumor Microenvironment |
| title | Tumor-induced pressure in the bone microenvironment causes osteocytes to promote the growth of prostate cancer bone metastases |
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