Bone Marrow-Derived Mesenchymal Stem Cells Differentiate into Cancer-Associated Fibroblasts and Promote Tumor Growth in Renal Cell Carcinoma

Background: Tumor–stroma interactions play a critical role in renal cell carcinoma (RCC) progression. Cancer-associated fibroblasts (CAFs) are considered key components of the tumor microenvironment; however, their origin remains controversial. This study aimed to determine whether bone marrow-derived mesenchymal stem cells (MSCs) contribute to CAF-like stromal changes and RCC progression. Methods: An orthotopic xenograft mouse model was established using luciferase- and GFP-labeled Caki-1 cells. MSCs labeled with PKH26 were administered intravenously. Tumor growth was evaluated using an in vivo imaging system and tumor volume measurements. Immunohistochemical analyses were performed to assess MSC localization and α-smooth muscle actin (α-SMA) expression. In vitro proliferation and migration assays were conducted using direct and indirect co-culture systems. Results: The intravenous administration of MSCs significantly increased tumor growth and bioluminescence intensity in an orthotopic model. The tumor volumes were significantly larger in the MSC-treated versus control group. An immunofluorescence analysis demonstrated partial co-localization of PKH26-labeled MSCs with α-SMA-positive fibroblast-like cells, suggesting acquisition of CAF-like features. Direct co-culture with MSCs significantly enhanced RCC cell proliferation and migration in vitro, whereas culturing in conditioned medium alone did not produce similar effects. Conclusions: Exogenously administered bone marrow-derived MSCs may be recruited into RCC tissues and acquire CAF-like features through interactions with tumor cells. These findings suggest that stromal–tumor cell interactions within the tumor microenvironment may contribute to RCC progression and represent a potential therapeutic target.