FIGURE 1.

Illustration of the morphology and proliferative status of cells in multicellular spheroids of the EMT6/Ro cell line. (A) Histological cross-section (optical microscopic image) through the center of a spheroid ∼1200 μm in diameter stained with eosin and hematoxalin, showing the viable rim of cells (red) and the necrotic center (orange). (B) Diagram illustrating the relative distributions of proliferating (green, P) and quiescent (red, Q) cells and central necrosis (gray, N) in a spheroid, relative to the gradients in nutrients and waste products. There is not actually a sharp demarcation between proliferating and quiescent cells as is the case for viable/necrotic boundary; rather, the fraction of proliferating cells decreases continuously across the viable cell rim.