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Establishment of xenografts of urological cancers on chicken chorioallantoic membrane(CAM)to study metastasis

Precision Clinical Medicine 2019年第3期2卷 140-151页

作者： Junhui Hu moe ishihara Arnold IChin Lily Wu Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California at Los AngelesCA 90095USA Department of Urology David Geffen School of MedicineUniversity of California at Los AngelesCA 90095USA Department of Pediatrics David Geffen School of MedicineUniversity of California at Los AngelesCA 90095USA Jonsson Comprehensive Cancer Center David Geffen School of MedicineUniversity of California at Los AngelesCA 90095USA

Cancer of the urological system commonly occurs in the kidney,bladder,and prostate *** clear cell subtype of renal cell carcinoma(ccRCC)constitutes the great majority of kidney *** ccRCC portends a very poor outcome with no effective treatment *** cancer is the most common cancer in males in the *** recent advances in selective kinase inhibitors and immunotherapies,the rate of developing new treatment from bench to bedside is slow.A time-consuming step is at the animal drug testing stage,in which the mouse model is the gold *** the pursuit to streamline the in vivo cancer biology research and drug development,we explored the feasibility of the chicken chorioallantoic membrane(CAM)model to establish *** CAM model greatly shortens the time of tumor growth and lowers the cost comparing to immunocompromised *** generated CAM xenografts from ccRCC,bladder and prostate cancer,with established cancer cell lines and freshly isolated patient-derived tissues,either as primary tumor cells or small pieces of *** successful CAM engraftment rate from the different tumor sources is 70%or *** our previously established metastatic ccRCC mouse model,we showed that the CAM xenograft maintains the same tumor growth pattern and metastatic behavior as observed in *** together,CAM can serve as a valuable platform to establish new patient-derived xenografts(PDXs)to study tumor biology,thus accelerating the development of individualized treatment to halt the deadly metastatic stage of cancer.

关键词： chorioallantoic membrane prostate cancer bladder cancer kidney cancer animal mode

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Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2329-2344页

作者： Junhui Hu Ping Tan moe ishihara Nicholas ABayley Shiruyeh Schokrpur Jeremy GReynoso Yangjun Zhang Raymond JLim Camelia Dumitras Lu Yang Steven MDubinett Parmjit SJat Jacques Van Snick Jiaoti Huang Arnold IChin Robert MPrins Thomas GGraeber Hua Xu Lily Wu Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Urology West China HospitalChengduChina Department of Hematology and Oncology University of California San DiegoSan DiegoCA92103USA Department of Neurosurgery David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Department of Biological Repositories Department of UrologyZhongnan Hospital of Wuhan UniversityWuhanChina Department of Medicine David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Jonsson Comprehensive Cancer Center David Geffen School of Medicine at UCLAUniversity of California Los AngelesLos AngelesCA90095USA MRC Prion Unit at UCL Institute of Prion Diseases33 Cleveland StreetLondonW1W 7FFUK Ludwig Institute for Cancer Research Ltd BrusselsBelgium Department of Pathology Duke UniversityDurhamNCUSA Department of Urology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCA90095USA Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center WuhanChina

Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under *** study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic *** VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)*** tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic *** tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic *** poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+***(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular *** deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical *** work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

关键词： VHL metastasis motility

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