Partial hepatectomy promotes implanted mouse hepatic tumor growth by activating hedgehog signaling

Objective: To investigate the role hedgehog signaling (Hh) in the growth of implanted hepatic tumors after partial hepatectomy (PH) in mice.

Methods: H22 cells were implanted to the scapula of 2 BALB/c (nu/nu) nude mice and tumor developed in 2 weeks. 40 nude mice were randomized into 4 groups: non-hepatectomy group (Sham operation group), 30% hepatectomy group, 70% hepatectomy group, and 70% hepatectomy with cyclopamine (Hh inhibitor). The hepatectomy model of nude mice was established. After hepatectomy, the tumor tissues incised from the scapula were implanted to the rest of the livers of the 4 groups. After 2 weeks, the tumor formation rates and the volumes of the implanted tumors were compared. Hh related proteins and downstream cytokine VEGF were tested by Western blot and Immunohistochemistry. All the data were analyzed to explore the role of Hh in the growth of tumor after PH.

Results: The volumes of the implanted tumors after liver resection were significantly higher in the 70% PH group than those in 0% and 30% PH groups; meanwhile, we also found that expression of the Hh ligand Indian Hh, its downstream transcription factor protein Gli-1, and its target VEGF were remarkably increased after PH, especially in the 70% PH group. Additionally, applying the Hh inhibitor cyclopamine to mice that underwent 70% PH significantly inhibited the growth of implanted tumors.

Conclusions: The Hh signaling pathway was activated after PH and promoted liver regeneration. The growth of implanted hepatic tumors was also accelerated after PH via paracrine signaling.