Fig. 6

Docetaxel treatment increases expression of pro-lymphangiogenic cytokines in 4T1 tumors. a Heat map representation of expression of chemokines associated with lymphangiogenesis (left) and corresponding known roles in cancer and lymphangiogenesis (right). Results obtained by flow cytometry analysis of 4T1 tumors treated as outlined in Fig. 2 (n = 4/group). Log-transformed data displayed as fold change and heat map generated using MatLab software. (*) indicates analysis by ELISA. Docetaxel abbreviated as DTX and anti-VEGFR3 therapy abbreviated as α-V3 in figure. b Proposed mechanism by which docetaxel results in lymphatic activation and the resulting effect on cancer cell response to therapy. (1) Docetaxel induces production of pro-lymphangiogenic factors in the breast tumor microenvironment. (2) Docetaxel-induced lymphangiogenic factors like VEGFC and TNFa result in VEGFR3-dependent enlargement of lymphatics (brown) and lymphangiogenesis. (3) Docetaxel-activated lymphatics promote VEGFR3-mediated tumor cell (green) invasion and (4) reduce docetaxel efficacy