Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer
J. Clin. Invest. Ahmed Boucharaba, et al. 114:1714 doi:10.1172/JCI22123 [Go to this article.]

Figure 4
Effect of LPA₁ overexpression in MDA-BO2 cells on osteolytic lesions and on skeletal and subcutaneous tumor growth. (A) Animals fed without or with doxycycline were inoculated intravenously with MDA-BO2 or clone no. 3 cells. (Upper panels) Representative radiographs of hind limbs from mice bearing MDA-BO2 or clone no. 3 cells 30 days after tumor cell inoculation. In the absence of doxycycline, there was a marked increase in the extent of osteolytic lesions (arrows) in mice bearing clone no. 3 cells. (Lower panels) Representative bone histology of Goldner’s trichrome–stained tibial metaphysis from metastatic animals. Bone is stained in green; bone marrow and tumor cells are stained red. Trabecular bone was completely destroyed and replaced by tumor cells (T) in tibial metaphysis from untreated animals bearing clone no. 3 cells. Scale bar: 1 mm. (B) Animals fed without (open symbols) or with (filled symbols) doxycycline were inoculated subcutaneously into the flank with MDA-BO2 (triangles), clone no. 3 (circles), or clone no. 79 (squares) cells. Tumors were measured at the indicated time points. V (in mm³) is expressed as the mean ± SD of 9 animals per group. P < 0.05; **P < 0.005 doxycycline-free versus doxycycline-fed tumor-bearing animals. (C) Subcutaneous (upper panels) and skeletal (lower panels) tumor tissue sections immunostained with an antibody against the nuclear Ki-67 antigen. The mitotic index (numbers on each panel) was calculated as the percentage of nuclei positive for Ki-67. Results are the mean ± SD of 6 independent tumor sections. ^#P < 0.0001 doxycycline-free versus doxycycline-fed tumor-bearing animals. Scale bars: 100 μm.