TY - JOUR
T1 - Localization of osteoblast inflammatory cytokines MCP-1 and VEGF to the matrix of the trabecula of the femur, a target area for metastatic breast cancer cell colonization
AU - Bussard, Karen M.
AU - Okita, Noriaki
AU - Sharkey, Neil
AU - Neuberger, Thomas
AU - Webb, Andrew
AU - Mastro, Andrea M.
N1 - Funding Information:
Acknowledgments This work was supported by the U.S. Army Medical and Material Research Command Breast Cancer Program (DAMD 17-02-1-0358 and W81XWH-06-1-0432 to AMM, W81XWH-06-1-0363 to KMB); National Foundation for Cancer Research, Center for Metastasis Research; and The Susan G. Komen Breast Cancer Foundation, BCTR0601044, BCTR104406. The authors would like to thank Jianwen Wei and Donna Sosnoski for their assistance.
PY - 2010/5
Y1 - 2010/5
N2 - Bone likely provides a hospitable environment for cancer cells as suggested by their preferential localization to the skeleton. Previous work has shown that osteoblast-derived cytokines increased in the presence of metastatic breast cancer cells. Thus, we hypothesized that osteoblast-derived cytokines, in particular IL-6, MCP-1, and VEGF, would be localized to the bone metaphyses, an area to which breast cancer cells preferentially traffic. Human metastatic MDA-MB-231 breast cancer cells were inoculated into the left ventricle of the heart of athymic mice. Three to four weeks later, tumor localization within isolated femurs was examined using μCT and MRI. In addition, IL-6, MCP-1, and VEGF localization were assayed via immunohistochemistry. We found that MDA-MB-231 cells colonized trabecular bone, the area in which murine MCP-1 and VEGF were visualized in the bone matrix. In contrast, IL-6 was expressed by murine cells throughout the bone marrow. MDA-MB-231 cells produced VEGF, whose expression was not only associated with the breast cancer cells, but also increased with tumor growth. This is the first study to localize MCP-1, VEGF, and IL-6 in bone compartments via immunohistochemistry. These data suggest that metastatic cancer cells may co-opt bone cells into creating a niche facilitating cancer cell colonization.
AB - Bone likely provides a hospitable environment for cancer cells as suggested by their preferential localization to the skeleton. Previous work has shown that osteoblast-derived cytokines increased in the presence of metastatic breast cancer cells. Thus, we hypothesized that osteoblast-derived cytokines, in particular IL-6, MCP-1, and VEGF, would be localized to the bone metaphyses, an area to which breast cancer cells preferentially traffic. Human metastatic MDA-MB-231 breast cancer cells were inoculated into the left ventricle of the heart of athymic mice. Three to four weeks later, tumor localization within isolated femurs was examined using μCT and MRI. In addition, IL-6, MCP-1, and VEGF localization were assayed via immunohistochemistry. We found that MDA-MB-231 cells colonized trabecular bone, the area in which murine MCP-1 and VEGF were visualized in the bone matrix. In contrast, IL-6 was expressed by murine cells throughout the bone marrow. MDA-MB-231 cells produced VEGF, whose expression was not only associated with the breast cancer cells, but also increased with tumor growth. This is the first study to localize MCP-1, VEGF, and IL-6 in bone compartments via immunohistochemistry. These data suggest that metastatic cancer cells may co-opt bone cells into creating a niche facilitating cancer cell colonization.
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U2 - 10.1007/s10585-010-9330-3
DO - 10.1007/s10585-010-9330-3
M3 - Article
C2 - 20446021
AN - SCOPUS:77953953240
SN - 0262-0898
VL - 27
SP - 331
EP - 340
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 5
ER -