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. 2023 Mar 16;3(3):444–458. doi: 10.1158/2767-9764.CRC-22-0480

FIGURE 7.

FIGURE 7

Germline deletion of PlexinB1 decreases metastasis in Ptenfl/flKrasG12V and Ptenfl/flp53fl/fl mice. A, Schematic diagram of generation of Ptenfl/flKrasG12VPlxnB1−/− and Ptenfl/flp53fl/flPlxnB1−/− mice. B, H&E staining of Ptenfl/flKrasG12VPlxnB1−/− prostate (scale bar: 200 μm). C and D, Invasive adenocarcinoma in prostates of Ptenfl/flp53fl/flPlxnB1−/− mice at day 100 timepoint showing sarcomatoid deposits next to epithelium (marked with arrow), scale bar: 500 μm (C), 100 μm (D). Sarcomatoid tumors from prostates of 6-month-old Ptenfl/flp53fl/flPlxnB1−/− mice. Scale bar: 500 μm (E), 50 μm (F). G, Kaplan–Meier survival curves for Ptenfl/flKrasG12V (n = 20), and Ptenfl/flKrasG12VPlxnB1−/− (n = 28), cohorts. Primary prostate tumor growth was the major reason for euthanasia. H, Kaplan–Meier survival curves for Ptenfl/flp53fl/fl (n = 30) and Ptenfl/flp53fl/flPlxnB1−/− (n = 21) cohorts. I and J,PlxnB1 germline deletion suppress metastasis in Ptenfl/flKrasG12V mouse model of prostate cancer. Mice were categorized according to their metastatic outcome: no metastatic deposits (white), lymph node metastasis (orange), both lymph node and lung metastasis combined with invasion into peritoneum or pelvic muscle (black). I, Percentages of animals with metastases in Ptenfl/flKrasG12V cohorts. J, Timing and type of metastatic deposits in Ptenfl/flKrasG12V (n = 20), and Ptenfl/flKrasG12V PlxnB1−/− mice (n = 28). K and L, PlxnB1 germline deletion suppress metastasis in Ptenfl/flp53fl/fl mouse model of prostate cancer. K, Percentage of mice with metastases in Ptenfl/flp53fl/fl cohorts: no metastatic deposits (white), invasion into peritoneum or pelvic muscle (blue), lymph node metastasis combined with invasion into peritoneum or pelvic muscle (purple). L, Timing and type of metastatic deposits in Ptenfl/flp53fl/fl (n = 30) and Ptenfl/flp53fl/flPlxnB1−/− (n = 21) mice. See Table 1 for statistical analyses. M and N,PlxnB1 deletion decreases local invasion by prostate tumor cells. Immunostaining of prostates of 100-day-old mice with cytokeratin AE1/AE3 (pan-cytokeratin) to identify prostate epithelial cells breaking basement membrane and invading stroma in Ptenfl/flKrasG12V (M) and Ptenfl/flp53fl/flPlxnB1−/− (N) mice. Scale bars, 50 μm. Graphs show quantitation of invasion in the Ptenfl/flKrasG12V and Ptenfl/flp53fl/fl backgrounds—Pan-cytokeratin positive cells breaking the basement membrane or located inside the stromal compartment were counted and divided by total number of pan-cytokeratin positive cells. *, P < 0.05 (t test, n = 3, mean ± SD).