Fig. 4.

Tumor dissemination correlates with vascularity of the tumor but not tumor growth/regression rate. A Cartoon illustrating dissemination of tumor cells (shown in orange) to the caudal hematopoietic plexus (marked by the black squares) three days following tumor implantation in the perivitelline space. B Representative images of tumor cells (shown in red) in the caudal hematopoietic plexus three days after tumor implantation for a representative model in which dissemination was moderately but significantly inhibited by treatment with Erlotinib (10 mg/L, right panels) but not by treatment with Paclitaxel (20 mg/L, left panels). C Quantification of the average number of cells that at three days post implantation have disseminated to the caudal hematopoietic plexus (metastasized cells) for each of the implantable models. D-F Quantification of the EMT-score (D), stromal content (E) and vascularity (F) of the PDX models when grown in mice plotted against the average number of metastasized cells, as quantified in C, three days after implantation of the models in zebrafish larvae. Positive correlation was significant for metastasis and vascularity but not for metastasis and EMT-score or stromal content. n = 12–33 per group. G Quantification of the relative change in metastasis to the caudal hematopoietic plexus in treatment compared to vehicle groups after treatment with either Erlotinib (10 mg/L, shown in light blue), or Paclitaxel (20 mg/L, shown in orange). Red dashed line indicates the control group for each model. n = 7–22 per group. H-J Quantification of the changes in tumor size between day three and zero for larvae in the control group (H) or after treatment with Erlotinib, 10 mg/L (I), or Paclitaxel, 20 mg/L (J), divided by the changes in tumor size between day three and zero for larvae in the corresponding control groups (anti-tumor efficacy) and plotted against the relative change in metastasis as quantified in G, for each of the 25 implantable models. A non-significant trend towards a positive correlation was observed in the Erlotinib treated group but not in the Paclitaxel treated groups. n = 7–22 per group