Abstract 400: Modulation of the metastatic microenvironment by soluble factors released by lung adenocarcinoma cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Soluble factors from primary tumors can modify target organs for metastasis through mobilization of bone marrow derived cells (BMDCs), which are recruited to tumors and to metastatic target organs and facilitate tumor growth and metastasis. Here we aimed to study early cellular and molecular events occurring in the lung, the metastatic target organ of the murine lung adenocarcinoma cell line LP07. We assessed by flow cytometry the numbers of BMDC positive for VEGFR1, SCF, CD34 or CXCR4 and the numbers of myeloid suppressor cells (CD11b+/Gr1+) and regulatory T cells (CD4+/CD25+/FOXP3+) in single cell lung suspensions obtained from 15-day tumor-bearing and control mice. Control and tumor-conditioned lungs of inoculated mice showed comparable amounts of these cell populations. To assess whether the primary tumor stimulates subsequent formation of macroscopic metastasis, mice bearing an intraperitoneal millipore chamber -that allows the diffusion of soluble molecules but not cell extravasation- loaded with LP07 cells or medium, were challenged with a LP07 intravenous inoculum at day 15. The presence of LP07 loaded chambers decreased the number of lung metastases three weeks after the inoculum compared to control mice (p≪0.05). In a different approach, mice were daily injected for 15 days with LP07 conditioned medium or control medium, and then challenged with a LP07 intravenous inoculum. When evaluated at day 21 post LP07 cell inoculation, the number of metastatic lung nodules was significantly lower (p≪0.05) in the group treated with LP07 conditioned medium. Besides, when we assessed matrix metalloproteinase (MMP) activity in lung homogenates from 15 day-tumor bearing and control mice, we found a significant increase in MMP-9 activity (p≪0.05) as assessed by semi-quantitative zymography in lungs from tumor-bearing mice.In conclusion, in the LP07 lung adenocarcinoma model, tumor cells secrete soluble factors that induce certain changes in the metastatic target organ, as the increase of MMP-9 activity. Moreover, in this experimental metastatic approach, a decrease in metastasis development was observed; the mechanisms underlying this phenomenon deserve further investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 400. doi:10.1158/1538-7445.AM2011-400