BackgroundCancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer and has been implicated in cytoprotection and tumor promotion. This study aimed to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer.MethodsThe correlation between autophagy and CSCs and its clinical significance were analyzed using pancreatic cancer tissue microarrays. Genetic and pharmacological approaches were applied to explore the function of autophagy on CSC activity and gemcitabine resistance of pancreatic cancer cells in vitro and in vivo.ResultsLC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44, and CD133 in pancreatic cancer tissues. High coexpression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5, ATG7, and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation, and resistance to gemcitabine in vitro and in vivo. Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44, and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170–82, could effectively counteract OPN-induced autophagy and CSC activity. According to the histochemical results, pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/CD133 had poor survival.ConclusionsInduction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. Combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for pancreatic cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-015-0449-3) contains supplementary material, which is available to authorized users.

Expression of integrin β1 is regulated by the mechanical stiffness of the ECM, and correlates with the invasion and metastasis events of HCC in patients with cirrhosis.

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Relapsing level of prostate-specific antigen (PSA) after initial curative-intent local therapy for organ-confined prostate cancer is often the first sign of recurrence. However, PSA level recurrence does not enable accurate differentiation of locally recurrent tumor from metastatic disease or a combination of both. Metastatic prostate cancer most frequently involves bones and lymph nodes, followed by other organs such as the liver, lung, pleura, adrenal gland, ureter, peritoneum, penis, testis, and meninges. Conventional imaging including CT and bone scintigraphy has long been the standard of care but has limited sensitivity in depicting early local recurrence or metastatic disease. Multiparametric MRI has been shown to be more sensitive in detecting locally recurrent tumor in the prostatectomy bed as well as in situ recurrence in a prostate gland that has been treated with radiation therapy or thermal ablation. In addition, lesions detected with multiparametric MRI may be amenable to targeted biopsy for definitive diagnosis of recurrence. PET/ CT or PET/MRI using the U.S. Food and Drug Administration (FDA)-approved tracers carbon 11 choline or fluorine 18 fluciclovine has demonstrated markedly increased sensitivity and specificity for diagnosis of early metastatic disease such as small-volume lymph node metastasis, as have a range of investigational gallium 68 prostate-specific membrane antigen (PSMA) radioactive PET tracers. With recent advances in imaging modalities and techniques, more accurate early detection, localization, and characterization of recurrent prostate cancer have become possible. The authors present a contemporary review of the strengths and limitations of conventional and advanced imaging modalities in evaluation of patients with recurrent prostate cancer and a systematic review of the clinical and imaging features of locally recurrent and metastatic disease. ©