FIGURE 1.

Human PCa Exo^Hypoxic promotes MMPs activity in selective organs in male athymic nude mice. A, Male athymic nude mice were injected with PBS, Exo^Normoxic or Exo^Hypoxic (10 μg each, IP) on alternate days for 4 weeks. At the end, mice were injected with MMPsense 750 dye and imaged for fluorescence and X-ray by In Vivo Multispectral FX instrument. Representative images are shown for various groups (PBS, Exo^Normoxic and Exo^Hypoxic). Mice without MMPsense injection served as negative control (bottom panel). In each image, dye in an eppendorf tube served as a positive control. B, Forty eight hours after MMPsense 750 dye injection, mice were killed, various organs isolated and imaged for fluorescence by In Vivo Multispectral FX imaging instrument. Organs: 1. brain; 2. lymph nodes + salivary glands; 3. lung + heart; 4. liver; 5. spleen; 6. kidneys; 7. prostate + seminal vesicles + bladder; 8. bone. Organs from animal without MMPsense dye injection served as negative control (top, left panel), while dye in an eppendorf served as positive control (in top left and bottom right images). C, Mice were injected IP with PBS or ExoGlow labelled exosomes (Exo^Normoxic and Exo^Hypoxic) and various organs were imaged 24 hours later. Organs: 1. Brain; 2. Lung; 3. Heart; 4. Liver; 5.Spleen; 6. Kidney; 7. Prostate. Exo^Hypoxic, exosomes secreted under hypoxic condition; Exo^Normoxic, Exosomes secreted under normoxic condition; IP, intraperitoneal; MMP, matrix metalloproteinases; PBS, phosphate buffered saline; PCa, prostate cancer [Color figure can be viewed at wileyonlinelibrary.com]