BACKGROUND:In vitro experiments and mice models have confirmed the importance of Sprouty 2(Spry2) in inhibiting tumorigenesis and the progression of human cancer.However,the prognostic value of Spry2 in cancer patients remains unknown.This study is aimed to investigate the clinical relevance and prognostic significance of Spry2 expression in patients with hepatocellular carcinoma(HCC).METHODS:With samples from 240 randomly-selected HCC patients who underwent surgery,immunohistochemistry was used to investigate Spry2 expression on tissue microarrays.The correlation of Spry2 expression with survival was estimated by the Kaplan-Meier method and univariate/multivariate Cox proportional hazard regression analysis.Spry2,ERK and phospho-ERK expression in HCC cell lines was detected by Western blotting.RESULTS:Among the patients,86.3%(207 of 240) exhibited down-regulation of Spry2 expression.Patients negative for Spry2 showed poorer survival(P=0.002) and increased recurrence(P=0.003).Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients(HR=1.47;95% CI,1.02-2.08;P=0.037).Downregulation of Spry2 was associated with highly malignant phenotypes like vascular invasion and advanced tumor stages,and was positively correlated with the metastatic potential of HCC cell lines.CONCLUSION:In the era of molecular targeted therapy,the expression of Spry2 in HCC may have relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.
Kang Song,Qiang Gao,Jian Zhou,Shuang-Jian Qiu,Xiao-Wu Huang,Xiao-Ying Wang and Jia Fan Liver Cancer Institute, Zhongshan Hospitaland Institute of Biomedical Sciences , Fudan University, Shanghai 200032, China
Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous patients.To metastasize,t he malignant cells must detach from the primary tumor and migrate to secondary sites in the body through either blood or lymph circulation.Macrophages appear to be directly involved in tumor progression and metastasis.However,the role of macrophages in affecting cancer metast asis has not been fully elucidated.Here,we have utilized an emerging technique,namely in vivo flow cytometry(IVFC)to study the depletion kinetics of circulating prostate cancer cells in mice and determine how depletion of macrophages by the liposome encapsulated clodronate affects the depletion kinetics.Our results show diferent depletion kinetics of PC-3 cells between the macrophagedeficient group and the control group.The number of circulating tumor cells(CTCs)in the macrophage-deficient group decreases in a slower manner compared to the control mice group.The differences in depletion kinetics indicate that the absence of macrophages facilitates the stay of prostate cancer cells in circulation.In addition,our imaging data suggest that macrophages might be able to arrest,phagocytose and digest PC-3 cells.Therefore,phagocy tosis may mainly contribute to the de-pletion kinetic diferences.The developed methods elaborated here would be useful to study the relationship between macr ophages and tumor metastasis in small animal cancer models.
