Figure 2

Mesenchymal stem/stromal cells (MSCs) inhibit primary tumor growth but increase skin invasion and development of metastasis. SUM149 cells (5 × 10⁵) were injected bilaterally into the cleared mammary fat pad of SCID/Beige mice with or without MSCs (10% of total number of cells injected per mammary gland, see Scheme 1). Tumor growth and tumor-skin involvement were monitored and tumors were resected in a survival surgery when tumors reached a volume of 300 mm³. Development of metastases was monitored for 8 weeks post-resection of primary tumor. (A) Time for tumor first detection by palpation. Tumor latency of mice co-injected with 10% MSC is shorter than control group (0% MSC). ^** P = 0.002, Student’s t test. (B) Time to tumor development between palpable and a volume of 300 mm³. Tumor growth of mice co-injected with 10% MSC is slower than control group (0% MSC). ^*** P = 0.001, Student’s t test. (C) Tumor growth curves of 0% and 10% MSC groups prepared with average of tumor burden per mouse, showing a statistical difference between groups. ^* P = 0.02, Student’s t test. (D) Tumor growth curves of 0% and 10% MSC groups prepared with average of tumor volume per side of injection, showing inhibition of contralateral tumors via co-injection of 10% MSC. (E) Hematoxylin and eosin (H&E) staining of tumor section of left-sided tumor from 0% MSC group. (F) H&E staining of tumor section of right-sided tumor from 0% MSC group. (G) H&E staining of tumor section of left-sided (ipsilateral) tumor from 10% MSC group. (H) H&E staining of tumor section of right-sided (contralateral) tumor from 10% MSC group. Scale bar is 100 μm in all images. (I) Number of tumors that showed skin invasion. Tumors of SUM149 cells co-injected with 10% MSC invaded the skin of mouse more frequently than control SUM149 cells (0% MSC). ^* P = 0.02, Fisher’s exact test. (J) Metastasis-free survival curve. Blue line, 0% MSC; green line, 10% MSC. P = 0.05, log-rank test. Mice co-injected with 10% MSC developed more rapidly spontaneous metastasis after resection than control group.