These data demonstrate that RCC cells preferentially interact with osteoblasts and extracellular matrix components of the human bone marrow and show increased migration ability in response

to osteoblast-derived factors suggesting a possible mechanism for facilitated homing of RCC cells into bone. Poster No. 110 Tumor-Lymphatic Cross Talk Contributes to Tumor Progression and Invasion Jacqueline D. Shields 1 , Amine Issa1, Iraklis C. Kourtis1, Melody A. Swartz1 1 Institute for Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Changes in the immunological equilibrium and escape from immune surveillance are critical events for the progression of a developing Linsitinib concentration tumor. Likewise, tumor derived vascular endothelial

growth factor C (VEGF-C) is known to stimulate lymphatics at the tumor periphery and promote metastasis to draining lymph nodes. CCL19 and CCL21 are produced by both lymphatic endothelium and reticular stroma guiding antigen presenting cells (APCs) to LN and driving co-localization of CCR7+ APCs and naïve T cells within selleck kinase inhibitor the lymph node. Furthermore, we recently demonstrated that tumors use autologous CCL21 secretion and lymphatic function to escape a growing tumor. To this end, we investigated how lymphatic growth factors and lymph node chemokines influence the developing tumor-lymphatic microenvironment and ensuing immune response. We engineered tumor cells

to secrete different levels of CCL21 and VEGF-C. Using in vitro co-culture models and complementary in vivo studies we demonstrate that several tumor cell lines express functional VEGFR-3; hence tumor-derived VEGF-C could act autologously on tumor cells to promote their invasion through a 3D matrix, by increasing their motility and proteolytic activity. In addition to peritumoral lymphatic expansion, Sclareol tumor-secreted VEGF-C also increased CCL21 production by lymphatic endothelium. Increased tumor volumes were observed in these VEGF-C-overexpressing tumors compared with control counterparts and coincided with a switch in the inflammatory compartment towards a regulatory phenotype. A sustained loss of CCL21 at the tumor site permitted an effective tumor specific immune response to develop. These results indicate that modulation of the tumor-lymphatic microenvironment not only promotes metastasis through VEGF-C-CCL21 cross-talk strategies but is also necessary for manipulation and control of the anti-tumor immune response. Poster No.