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Purpose: This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer., Methods: We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin-CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model., Results: CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK-MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model., Conclusions: CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.

In a previous report, we showed that the relatively selective dopamine (DA) D-2 agonist bromocriptine (BRC), when combined with the selective D-1 agonist SKF38393, produced in DA-depleted mice a marked locomotor stimulation, despite BRC and SKF38393 being inactive by themselves (Jackson and Hashizume 1986). The present series of experiments was designed to further explore this interaction. In all experiments, mice were pretreated with reserpine and/or alpha methyl-p-tyrosine (AMPT). In mice pretreated with reserpine, AMPT or reserpine plus AMPT, BRC plus SKF38393 produced marked excitation whether the BRC was given 3 or 1 h prior to the SKF38393 challenge. However, while there was no absolute requirement that BRC be given a certain time before SKF38393, this factor was of some importance, with the onset of locomotor stimulation produced by the combination being much more rapid if the BRC was given 3 h rather than 1 h before the SKF38393. Interestingly, the degree of locomotor stimulation produced by the combination was always greatest in the animals premedicated with reserpine alone. If AMPT was also used (with or without reserpine), the stimulation produced by the combination was reduced, which may have resulted in part from a non-specific depressant effect of the AMPT. From these results, it seems as though endogenous DA is not required for BRC to work, provided that D-1 receptors are stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)

In mice pretreated with reserpine plus alpha-methyl-p-tyrosine, neither the D-2 selective agonist bromocriptine, nor the D-1 selective agonist SKF38393, produced any measurable increase in locomotion in mice. However, the combination of the two agonists produced a marked and dose-dependent increase in co-ordinated locomotor activity. In mice with their dopamine stores and dopamine synthesis intact, SKF38393 was inactive by itself, but significantly enhanced the stimulant effect produced by bromocriptine. The data suggest that bromocriptine requires concomitant stimulation of D-1 receptors for the full expression of its behavioural stimulant effects.