Figure 1
Pretreatment with conditioned medium from mesenchymal stem/stromal cells (MSC-CM) reduces tumor initiation and delays tumor growth but promotes skin invasion in an inflammatory breast cancer (IBC) xenograft model. SUM149 cells were cultured in vitro as mammospheres with and without MSC-CM for 5 days and then injected into the cleared mammary fat pad of SCID/Beige mice at two different dilutions: 1 × 105 and 2 × 104 (20 mice per group). Tumor initiation was monitored for 6 months. (A) Number of tumors observed in each group of injections. Tumor initiation of SUM149 cells following pretreatment with MSC-CM at permissive and restrictive cell dilutions is lower than control SUM149 cells. P = 0.04; ELDA. (B) Time to tumor initiation (palpable tumor). Blue line, control 1 × 105 cells; gold line, MSC-CM 1 × 105 cells; green line, control 2 × 104 cells; red line, MSC-CM 2 × 104 cells. *** P = 0.001, log-rank test. Tumor latency of SUM149 cells following pretreatment with MSC-CM (gold line) at a permissive cell dilution is longer than control SUM149 cells (blue line). (C) Time to tumor development between palpable and a volume of 300 mm3. Tumor growth of SUM149 cells following pretreatment with MSC-CM at a permissive cell dilution is slower comparing with control SUM149 cells. *** P = 0.001, Student’s t test. (D) Number of tumors that showed skin invasion in groups injected with 1 × 105 SUM149 cells. Tumors of SUM149 cells pretreated with MSC-CM invaded the skin of mice more frequently than control SUM149 cells. * P = 0.03, Fisher’s exact test. (E) Image of a mouse injected with SUM149 cells pretreated with MSC-CM showing gross skin involvement following primary tumor resection. (F) Image of same mouse as in E showing metastasis in the axilla by bioimaging of luciferase signal. (G and H) Hematoxylin and eosin (H&E) staining of tissue section from a mouse injected with 1 × 105 SUM149 cells pretreated with MSC-CM showing IBC characteristic dermal lymphovascular invasion (dermolymphatic tumor emboli). Scale bar is 200 μm in all images.