Fig. 7

Binding and RTK inhibition for blocking CIC-TEX activity as adjuvant PaCa therapy. Mice received an ot (A818.4-v6kd) or a sc (A818.4) tumor cell injection and weekly the RTK inhibitor GEM (iv) or anti-Tsp8 (CO029) (iv). a Survival time and mean survival time of v6kd-TB mice (intrapancreatic) treated with CIC-TEX (2x/wk) and GEM or CO029 (1x/wk). b Recovery of disseminated tumor cells in cultures of dispersed organs at autopsy. c Tumor growth rate, survival time and mean survival time of sc A818.4-TB mice, treated with GEM or CO029; d disseminated tumor cell recovery in cultures of dispersed organs at autopsy; a-d p-values for the mean survival time and the numbers of organs containing dispersed tumor cells (after Bonferroni-Holm correction) of GEM- or CO029-treated compared to untreated v6kd-TB and CIC-TEX-treated-TB or wt-TB are indicated. e,g,i,k,l Flow-cytometry of dispersed tumor cells and BMC of untreated and GEM- or CO029-treated A818.4-TB mice evaluating CIC, angiogenic, apoptosis, proteolysis, adhesion (only tumor cells) marker expression and MDSC (CD11b + Gr1+) (only BMC); mean % stained cells±SD (3 mice), significant differences by GEM- or CO029-treatment: *. f,h,j Immunohistology of A818.4 shock-frozen tumor sections from untreated, GEM- or CO029-treated mice stained for CIC markers, VEGFR2, VEGFR3, CD31, MMP2 and TIMP1 (scale bar: 100 μm). GEM and CO029 weakly affect tumor growth and strongly tumor cell dissemination. Ex vivo analysis indicates that GEM and CO029 act independently. GEM primarily affects tumor cell apoptosis, proteases and MDSC expansion, CO029 treatment is accompanied by a reduction in (Tsp8-associated) CIC markers and compromises (lymph)angiogenesis