Different but synergistic effects of bone marrow-derived VEGFR2(+) and VEGFR2(−)CD45(+) cells during hepatocellular carcinoma progression

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality worldwide in men. Bone marrow-derived cells (BMDCs), including circulating endothelial progenitor cells, have been reported to be involved in the progression of HCC. The complexity of BMDCs inspires further interest in the study of HCC. In the present study, highly metastatic HCC models with BM function deficiency/reconstruction were established by sublethal irradiation/BM transplantation. The effects of vascular endothelial growth factor receptor-2 (VEGFR2)(+) or VEGFR2(−)/cluster of differentiation 45 (CD45)(+) BMDCs on HCC growth were evaluated. VEGFR2(+) and VEGFR2(−)CD45(+) BMDCs facilitated the recovery of BM function and promoted tumor growth, while the enhancement of tumor growth by VEGFR2(−)CD45(+) BMDCs was independent of VEGFR2(+) BMDCs. BM-derived CD45(+)CD133(+) and VEGFR2(+)CD133(+) cells synergistically played a role in the different stages during HCC progression. In conclusion, different types of BMDCs exhibit effects on HCC tumor growth in a coordinated manner.