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Suppression and Activation of the Malignant Phenotype by Extracellular Matrix in Xenograft Models of Bladder Cancer: A Model for Tumor Cell “Dormancy”

Figure 3

Histopathology of cells from flank xenografts.

Features identified histopathologically are shown as follows. Areas of malignant cells are outlined in black, and areas of coagulative necrosis are outlined in yellow. Black arrows illustrate apoptotic bodies. Yellow arrows identify mitotic figures. At the zoom level shown here these are difficult to distinguish but were identified under high power. (A) Cells co-injected with Matrigel that immediately presented a malignant growth pattern. The pathologic description noted large areas of coagulative necrosis with acute inflammation (the small, dense cells are neutrophils) with an area of highly atypical cells revealing marked nuclear pleomorphism, all indicative of high grade neoplasia. (B) Cells co-injected with SISgel that remained in the suppressed or dormant phenotype. This slide was read as cells with moderate cellular atypia and pleomorphism with minimal evidence of coagulative necrosis, mitosis and apoptosis. (C) Cells co-injected with SISgel that initially presented a suppressed phenotype for 8 weeks but then resumed growth in the malignant phenotype. This was read as containing an area of coagulative necrosis with acute inflammation and foci of markedly atypical cells along with prominent mitosis and apoptosis. Some fields contained multinucleated tumor giant cells usually indicative of high-grade neoplasia (D) Cells co-injected with Collagen I demonstrating a malignant growth pattern similar to those illustrated in panels A and C. All images are at 400X.

Figure 3

doi: https://doi.org/10.1371/journal.pone.0064181.g003