Figure 4

Mesenchymal stem/stromal cells (MSCs) increase the sensitivity of metastatic inflammatory breast cancer (IBC) xenografts to erlotinib. 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). Mice were treated with erlotinib diet (dose of 40 mg/kg per day). Treatment started on day 1 following injection of cells and ended 17 weeks later. Tumor growth was 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) Tumor growth curves of 0% MSC groups treated with and without erlotinib, prepared with average of tumor burden per mouse. Green arrow indicates when erlotinib treatment was discontinued. (B) Tumor growth curves of 10% MSC groups treated with and without erlotinib, prepared with average of tumor burden per mouse. Green arrow indicates when erlotinib treatment was discontinued. (C) Tumor growth curves of 0% and 10% MSC groups treated with erlotinib, prepared with average of tumor burden per mouse, showing no statistical difference between groups. P = NS, Student’s t test. Green arrow indicates when erlotinib treatment was discontinued. (D) Tumor growth curves of 0% and 10% MSC groups treated with erlotinib, prepared with average of tumor volume per side of injection, showing no difference between right side of 0% and 10% groups and left side of 0% and 10% groups. Green arrow indicates when erlotinib treatment was discontinued. (E) Tumor growth curves between weeks 15 and 19 of 0% and 10% MSC groups treated with erlotinib, prepared with average of tumor volume per side of injection, showing that erlotinib inhibited the effects promoted by MSC in the contralateral tumors. Erlotinib treatment was stopped at 17 weeks (green arrow). (F) Metastasis-free survival curve. Purple line, 10% MSC group treated with erlotinib diet; tan line, 0% MSC group treated with erlotinib diet; blue line, 0% MSC group treated with control diet; green line, 10% MSC groups treated with control diet. P = 0.001, log-rank test. Erlotinib treatment inhibited mice co-injected with 10% MSC to developed spontaneous metastasis after resection in comparison with 10% MSC untreated group.