The abnormally active tumor vasculature provides a good blood supply for the rapid proliferation of tumors.The tumor microenvironment of tumor cells is associated with the secretion of a lot of angiogenic factors to p...The abnormally active tumor vasculature provides a good blood supply for the rapid proliferation of tumors.The tumor microenvironment of tumor cells is associated with the secretion of a lot of angiogenic factors to promote the formation of blood vessels.However,the blood vessels are often irregular and immature.Additionally,the tumor tissue,in the process of its rapid proliferation,oppresses tumor blood vessels,causing hypoperfusion and leading to high interstitial pressure and hypoxia,which also results in changes to the fluid mechanics in the tumor microenvironment.Different fluid mechanics affect circulating tumor cell behavior and control various functions.A good mechanical microenvironment may be one of the important targets for inhibiting tumor proliferation and migration.Therefore,regulating tumor blood vessels to maintain a steady fluid mechanical microenvironment has the potential to be one of the key targets for tumor treatment.Numerous studies have demonstrated that certain natural medicines exhibit significant potential for inhibiting tumor growth and metastasis by selectively targeting tumor blood vessels,regulating the production of angiogenic cytokines,facilitating vascular normalization,etc.Furthermore,natural medicines enhance the anti-tumor effects of chemoradiotherapy and act as adjuvant agents to alleviate its associated side effects.This review summarizes the angiogenesis of the tumor microenvironment,changes induced by mechanical conditions,and the response of tumor cells and vasculature to different fluid shear stress to promote vascular normalization treatment strategies.展开更多
Leukemia stem cells in acute myeloid leukemia(AML)can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy.In the context of AML,endothelial cells(ECs)a...Leukemia stem cells in acute myeloid leukemia(AML)can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy.In the context of AML,endothelial cells(ECs)are crucial components of these niches that appear to promote malignant expansion despite treatment.To better understand these interactions,we developed a real-time cell cycle-tracking mouse model of AML(Fucci-MA9)with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse.We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells,leading to relapse and proliferation.Importantly,post-chemotherapy resting leukemia cells tended to localize closer to blood vessels.Mechanistically,after chemotherapy,resting leukemia cells interacted with ECs,promoting their adhesion and anti-apoptotic capacity.Further,expression analysis of ECs and leukemia cells during AML,after chemotherapy,and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs.These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.展开更多
基金supported by the Weifang Science and Technology Development Projects(Shandong,China)(No.2023YX092).
文摘The abnormally active tumor vasculature provides a good blood supply for the rapid proliferation of tumors.The tumor microenvironment of tumor cells is associated with the secretion of a lot of angiogenic factors to promote the formation of blood vessels.However,the blood vessels are often irregular and immature.Additionally,the tumor tissue,in the process of its rapid proliferation,oppresses tumor blood vessels,causing hypoperfusion and leading to high interstitial pressure and hypoxia,which also results in changes to the fluid mechanics in the tumor microenvironment.Different fluid mechanics affect circulating tumor cell behavior and control various functions.A good mechanical microenvironment may be one of the important targets for inhibiting tumor proliferation and migration.Therefore,regulating tumor blood vessels to maintain a steady fluid mechanical microenvironment has the potential to be one of the key targets for tumor treatment.Numerous studies have demonstrated that certain natural medicines exhibit significant potential for inhibiting tumor growth and metastasis by selectively targeting tumor blood vessels,regulating the production of angiogenic cytokines,facilitating vascular normalization,etc.Furthermore,natural medicines enhance the anti-tumor effects of chemoradiotherapy and act as adjuvant agents to alleviate its associated side effects.This review summarizes the angiogenesis of the tumor microenvironment,changes induced by mechanical conditions,and the response of tumor cells and vasculature to different fluid shear stress to promote vascular normalization treatment strategies.
基金National Natural Science Foundation of China(81890990)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-019)+1 种基金Chinese Academy of Medical Sciences Fundamental Research Funds for Central Research Institutes(3332021093)Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0016).
文摘Leukemia stem cells in acute myeloid leukemia(AML)can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy.In the context of AML,endothelial cells(ECs)are crucial components of these niches that appear to promote malignant expansion despite treatment.To better understand these interactions,we developed a real-time cell cycle-tracking mouse model of AML(Fucci-MA9)with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse.We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells,leading to relapse and proliferation.Importantly,post-chemotherapy resting leukemia cells tended to localize closer to blood vessels.Mechanistically,after chemotherapy,resting leukemia cells interacted with ECs,promoting their adhesion and anti-apoptotic capacity.Further,expression analysis of ECs and leukemia cells during AML,after chemotherapy,and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs.These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.
