CCL21 promotes the migration and adhesion of highly lymph node metastatic human non-small cell lung cancer Lu-99 in vitro.

To develop new therapy strategies for lung cancer, we established an animal model, which reflects the clinical features of mediastinal lymph node metastasis of lung cancer. This study was designed to determine whether CCL21 induced biological functions associated with the metastasis of highly lymph node metastatic human non-small cell lung cancer (NSCLC) selected by our model. Orthotopic intrapulmonary implantation of human NSCLC (Lu-99 and A549) was performed to analyze the metastatic characteristics of these cells.

RANKL-induced CCL22/macrophage-derived chemokine produced from osteoclasts potentially promotes the bone metastasis of lung cancer expressing its receptor CCR4.

Chemokines are now known to play an important role in cancer growth and metastasis. Here we report that differentiating osteoclasts constitutively produce CCL22 (also called macrophage-derived chemokine) and potentially promote bone metastasis of lung cancer expressing its receptor CCR4. We first examined expression of chemokines by differentiating osteoclasts.

Inhibition of lymphangiogenesis-related properties of murine lymphatic endothelial cells and lymph node metastasis of lung cancer by the matrix metalloproteinase inhibitor MMI270.

Based on a previous report on the effect of a matrix metalloproteinase (MMP) inhibitory compound, MMI270, in regulating tumor-induced angiogenesis, as well as recent findings concerning functional correlations among tumor metastasis, angiogenesis and lymphangiogenesis, we investigated the anti-metastatic efficacy of MMI270 in a murine model of lymph node metastasis of lung cancer, and analyzed whether this inhibitor could also regulate lymphangiogenesis-related properties of murine lymphatic endothelial cells (LECs) and invasive properties of Lewis lung cancer (LLC) cells. The observation that MMI270 led to a significant decrease in the weight of tumor-metastasized lymph nodes of mice led us to test its anti-lymphangiogenic and anti-invasive effects in vitro. Murine LECs were characterized by an in vitro tube formation assay, by semi-quantitative RT-PCR assay to examine the expression of mRNAs for flt-4, Flk-1, Tie-1, Tie-2, CD54/ICAM1, vWF, MMPs and uPA, and by western blotting to confirm the protein expression of flt-4 and CD31/PECAM.

Anti-tumor angiogenic effect of a matrix metalloproteinase inhibitor MMI270.

We investigated the anti-angiogenic effects of a matrix metalloproteinase inhibitor, (MMI), so called MMI270, against B16-BL6 melanoma through the inhibition of the migrating and invasive abilities of hepatic sinusoidal endothelial (HSE) cells, as well as the formation of tube-like structures by HSE cells. MMI270, at the concentration of 12.5 micrograms/ml, significantly inhibited the migration and invasion of HSE cells, in addition to tube formation by approximately 40%.