Figure 3

MAb 4C5 inhibits the metastatic deposition of MDAMB453 cancer cells into the lungs of SCID mice. MDAMB453 cells were labeled with the fluorescent dye DiI and injected into SCID mice, in the presence either of 100 μg/ml of mAb 4C5 or of an irrelevant antibody (control), as described in Methods. Evaluation of metastatic deposits was performed several hours later. (A) Macroscopic level: An important number of metastatic deposits (arrow) was observed in control animals as compared to mAb 4C5 treated mice. (B) Microscopic level: Representative cryosections of the lungs of control and mAb 4C5 treated mice. The arrows show MDAMB453 cells stained with DiI present in the lung tissue. A significant decrease in the deposition of cancer cells was observed in the mAb4C5 treated mice. (C) Quantitative effect of mAb 4C5 on the metastatic deposition of MDAMB453 cells into the lungs showed an 86.67% inhibition of the metastatic deposition in the mAb 4C5 treated mice when compared to the control animals. (D) A 3D reconstitution of a cryosection from a control animal: The arrow demonstrates infiltration of metastatic deposits in the lung tissue. (E) MDAMB453 cells restrained in the inner surface of large pulmonary vessels derived from mAb 4C5 treated mice. On the contrary, in the lungs from control mice MDAMB453 cells could rarely be detected stagnating in the inner surface of the pulmonary vessels. However, cancer cells were clearly observed dispersed in the lung tissue. Arrows indicate the pulmonary vessels. (F) Quantitative effect of mAb 4C5 on the retention of MDAMB453 cells in the pulmonary vessels. A 15.4% of the vessels visualized in the control animals showed intravascular cancer cell retention. In contrast in the mAb 4C5 treated mice, cancer cells were observed stagnating in the inner surface of 58.76% of the calculated vessels (p < 0.01 Bar, 40 μm).