Fig. 8
Inhibition of cathepsins in vivo results in abrogation of TMEM106B-mediated increase in lung metastasis. The Vector alone or TMEM106B-induced cells were injected subcutaneously into syngeneic hosts and treated daily with either Vehicle control (Placebo) or with 25 mg/kg of E64D. a qPCR analysis for TMEM106B expression in primary tumor tissue from mice of different cohorts as indicated. b–e Activity of indicated cathepsins were assessed using specific activity assays in tissue lysates from either primary tumors or liver in the different cohorts as indicated. f Observed primary tumor growth and g formation of metastatic nodules in lungs. h Representative H&E-stained lungs sections are shown from different cohorts as indicated. Lungs from mice injected with TMEM106B-induced cells show significantly more incidence of lung metastasis which are abrogated upon treatment with E64D. All asterisks indicate statistical significance by t test (n ≥ 3, *p ≤ 0.05)
