Figure 1.

Melanoma Cells Respond to PLX4720 Heterogeneously In Vivo

(A and B) Growth curves of the indicated melanoma cells in vitro (A) and in vivo (B) treated with DMSO (0.1% in vitro and 4% in vivo) or PLX4720 (1 μM in vitro and 25 mg/kg in vivo). Data in (A) are represented as mean ± SD.

(C and D) Intravital longitudinal imaging of 5555-EKAREV-NLS tumors through an imaging window. The mouse was gavaged PLX4720 (25 mg/kg) every 24 hr, and images were acquired before and 4 hr after the first, second (Day 1), and third (Day 2) gavage. ERK activities in (D) were quantified and shown as mean ± SD. Scale bars represent 100 μm.

(E) Intravital images of 5555-EKAREV-NLS subcutaneously grown in C57BL/6_ROSA26-mTmG mice. Upper and lower images are from mice treated with DMSO and PLX4720 for 3 days, respectively. Left: all host cells (Tomato). Right: ERK activity in 5555 cells. Scale bars represent 500 μm.

(F) Distribution and histogram of ERK activity in control and PLX4720-treated mice. In PLX4720-treated mice, cells are separated into two groups according to the host cell density (low and high stroma) and analyzed.

Bars in the scatterplots indicate mean ± SD. See also Figure S1.