Supported by the National Natural Science Foundation of China,a collaborative study by the laboratories of Dr.Hu Guohong(胡国宏)from Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences and Dr.Yang ...Supported by the National Natural Science Foundation of China,a collaborative study by the laboratories of Dr.Hu Guohong(胡国宏)from Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences and Dr.Yang Qifeng(杨其峰)from Shangdong University demonstrates that Dickkopf1(DKK1)展开更多
Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients...Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.展开更多
文摘Supported by the National Natural Science Foundation of China,a collaborative study by the laboratories of Dr.Hu Guohong(胡国宏)from Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences and Dr.Yang Qifeng(杨其峰)from Shangdong University demonstrates that Dickkopf1(DKK1)
基金This work was sponsored by grants from the National Natural Science Foundation of China(81803269 and 81427805)the Science and Technology Commission of Shanghai Municipality(18YF1412100 and 2019Y0150)+2 种基金the National Key Research and Development Program of China(2018YFC2000700)the Key Research Program of the Chinese Academy of Sciences(ZDRW-ZS-2017-1)Shanghai Municipality Health Commission(GWV-10.2-YQ17 and 2019Y0150).
文摘Rapid metastasis to vital organs such as the lung,liver,and brain is responsible for the vast majority of pancreatic cancer deaths.Liver metastasis of pancreatic cancer accounts for the high mortality rate in patients.Exosomes derived from pancreatic cancer cells tend to be enriched in proteins that are anchored to the cell membrane,supporting the reprogramming of the tumor microenvironment and the progression of distant metastatic lesions.For the first time,our study has demonstrated that cluster of differentiation 44(CD44),a transmembrane glycoprotein delivered by exosomes,is involved in the metastatic process of pancreatic cancer.Moreover,CD44 was found to interact with integrin a6b4 to form a complex,thereby remodeling intracellular skeleton proteins,and to promote tumor cell motility through the activation of the Src and Ras signaling cascades.Notably,we also demonstrated that the CD44–a6b4 complex can be delivered to the target region via the paracrine effects of exosomes.The selective uptake of CD44-competent tumor exosomes by liver cells activated fibrotic pathways and generated a pre-metastatic niche by stimulating the cytokines,proinflammatory factors,and growth factors that ultimately support tumor metastasis.Our results suggest the potential application of exosomal CD44 as a biomarker for the clinical diagnosis of and therapy for pancreatic cancer.