Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. Prognosis for ccRCC is generally poor since it is largely resistant to chemo- and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/TICs isolated from established RCC cell lines - basic ccRCC research model - has never been investigated in vivo. CD105+, CD105-, CD44+ and CD44- as well as CD44-/CD105- CD44+/CD105+ and CD44-/CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into NOD SCID mice and tumor growth was monitored with MRI and PET/CT. Tumor growth was observed after implantation of CD105+, CD44+, CD44-, CD44-/CD105+ and CD44-/CD105- but not CD105- or CD44+/CD105+. Implantation of CD44-/CD105- cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44- tumors expresses Nanog and Oct-4, while CD44- tumors additionally expressed endothelial cell marker - CD31.