Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for spr...Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.展开更多
The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma(HCC) wher...The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma(HCC) where alternate therapies are lacking. We recently published a paper entitled "Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma" in the Journal of the National Cancer Institute, providing a potential explanation for this limited beneit. We found that in mice bearing HCCs that had acquired resistance to sorafenib, tumors had switched from using angiogenesis for growth to co-opting the liver vasculature by becoming more invasive. Accumulating evidence suggests that many human tumor types may use vessel co-option, which has profound implications for the use of anti-angiogenic agents for cancer treatment.展开更多
The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels an...The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels and cancer.Tumors need blood perfusion but there are mounting evidences that angiogenesis alone does not explain it in all the neoplasms.In this editorial,for a special issue on tumor and vessels published in the Chinese Journal of Cancer,we briefly introduce the history of the evidences that solid tumors can sometimes obtain blood perfusion by alternative approaches other than sprouting angiogenesis,i.e.,vessel co-option and vasculogenic mimicry.This editorial provides also the links to several most recently published discoveries and hypotheses on tumor interaction with blood vessels.展开更多
Liver is the most common site of metastases of colorectal cancer,and liver metastases present with distinct histopathological growth patterns(HGPs),including desmoplastic,pushing and replacement HGPs and two rare HGPs...Liver is the most common site of metastases of colorectal cancer,and liver metastases present with distinct histopathological growth patterns(HGPs),including desmoplastic,pushing and replacement HGPs and two rare HGPs.HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics.Many studies have revealed the association of HGPs with carcinogenesis,angiogenesis,and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications.These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making,and a target of imaging observation for patient screening.Of note,it is crucial to determine the underlying mechanism shaping HGP,for instance,immune infiltration and extracellular matrix remodeling in desmoplastic HGP,and aggressive characteristics and special vascularization in replacement HGP(rHGP).We highlight the importance of aggressive features,vascularization,host immune and organ structure in formation of HGP,hence propose a novel"advance under camouflage"hypothesis to explain the formation of rHGP.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81472386,81472380,81272340,and 81030043)the National High Technology Research and Development Program of China (863 Program,No.2012AA02A501)
文摘Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen,nutrients,and other essential factors.The well-known vascular endothelial growth factor(VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature,which has become therapeutic targets in clinical practice.However,the survival benefits gained from targeting VEGF signaling have been very limited,with the inevitable development of treatment resistance.In this article,we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy,with a special focus on vessel co-option,vessel remodeling,and tumor cell-derived vasculature establishment.Vessel co-option may occur in tumors independently of sprouting angiogenesis,and sprouting angiogenesis is not always required for tumor growth.The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced.The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.
文摘The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma(HCC) where alternate therapies are lacking. We recently published a paper entitled "Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma" in the Journal of the National Cancer Institute, providing a potential explanation for this limited beneit. We found that in mice bearing HCCs that had acquired resistance to sorafenib, tumors had switched from using angiogenesis for growth to co-opting the liver vasculature by becoming more invasive. Accumulating evidence suggests that many human tumor types may use vessel co-option, which has profound implications for the use of anti-angiogenic agents for cancer treatment.
文摘The limited clinical benefits from current antiangiogenic therapy for cancer patients have triggered some critical thoughts and insightful investigations aiming to further elucidate the relationship between vessels and cancer.Tumors need blood perfusion but there are mounting evidences that angiogenesis alone does not explain it in all the neoplasms.In this editorial,for a special issue on tumor and vessels published in the Chinese Journal of Cancer,we briefly introduce the history of the evidences that solid tumors can sometimes obtain blood perfusion by alternative approaches other than sprouting angiogenesis,i.e.,vessel co-option and vasculogenic mimicry.This editorial provides also the links to several most recently published discoveries and hypotheses on tumor interaction with blood vessels.
基金Supported by National Nature Science Foundation,No.81873111,No.82174454,and No.82074182Natural Science Foundation of Beijing,No.7202066。
文摘Liver is the most common site of metastases of colorectal cancer,and liver metastases present with distinct histopathological growth patterns(HGPs),including desmoplastic,pushing and replacement HGPs and two rare HGPs.HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics.Many studies have revealed the association of HGPs with carcinogenesis,angiogenesis,and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications.These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making,and a target of imaging observation for patient screening.Of note,it is crucial to determine the underlying mechanism shaping HGP,for instance,immune infiltration and extracellular matrix remodeling in desmoplastic HGP,and aggressive characteristics and special vascularization in replacement HGP(rHGP).We highlight the importance of aggressive features,vascularization,host immune and organ structure in formation of HGP,hence propose a novel"advance under camouflage"hypothesis to explain the formation of rHGP.
