Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer.
Bottom Line: New effective therapeutic strategies are greatly needed.In contrast, inhibiting the effector Smo decreased the anchor-dependent and anchor-independent proliferation.These results suggest that Hh signaling is elevated in GBC and may be involved in the acquisition of malignant phenotypes, and that Hh signaling may be a potential therapeutic target for GBC.
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.Show MeSH
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Mentions: First, we evaluated the expression of Hh pathway components in GBC tissues from patients by immunohistochemistry. The ratio of female to male patients was 1.2:1.0 (20 women, 17 men). Distribution according to the stage of the UICC was: IA, n = 8; IB, n = 18; IIA, n = 2; IIB, n = 8; III, n = 1. Median age at time of diagnosis was 67 years; 68 years (range, 53–83 years) for men and 66 years (range, 42–85 years) for women (Table S2). The expression of Gli1 was detected in the nucleus of cancer cells in 19/37 (51.3%) GBCs (Fig.1a, red arrows), which suggests that Hh signaling is activated in GBC. Both Shh and Smo expression were also detected in 17/37 (45.9%) and 24/37 (64.9%) of the GBCs, respectively. The subcellular localization of Shh and Smo were mainly cytoplasmic in cancer cells (Fig.1a). Gli1 was not detected in the nuclei of normal gallbladder cells. The expression of Shh and Smo was notably elevated in GBC tissues versus normal gallbladder tissues where they were virtually undetectable (Fig.1b). These results suggest that Hh signaling is active in GBC and may play an important role in disease progression and severity.
Affiliation: Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.