title: Subpopulations of uPAR+ contribute to vasculogenic mimicry and metastasis in large cell lung cancer.
abstract: The urokinase plasminogen activator receptor (uPAR) is closely associated with poor prognosis in various aggressive cancers including large-cell lung cancer (LCLC). Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks involving the blood supply in early tumor formation. We demonstrate the statistically positive correlation of uPAR expression with VM formation, metastasis, and poor prognosis of LCLC patients. uPAR(+) cells sorted from the LCLC H460 cell line show higher invasion, migration capacity, and tube structure formation capability on Matrigel compared with uPAR(-) cells. uPAR(+) tumor cells highly expressed vimentin and VE-cadherin; the epithelial marker E-cadherin was low expressed. Higher EMT-regulated protein twist and snail expressions were also observed in these cells. uPAR(+) cells injected subcutaneously into nude mice markedly increased tumor growth, induced VM formation and liver metastasis; by contrast, uPAR(-) cells did not. The data suggest that uPAR expression may predict VM formation, tumor metastasis and poorer prognosis of LCLC patients. The uPAR gene may be used as a novel therapeutic target for inhibiting angiogenesis and metastasis in LCLC.
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Electronic address: dylylnj@163.com.
authors: Yanlei
authors: Y
authors: Li
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: baocunsun@gmail.com.
authors: Baocun
authors: B
authors: Sun
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: tianjinzhaoxiulan@163.com.
authors: Xiulan
authors: X
authors: Zhao
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: drddzh@163.com.
authors: Danfang
authors: D
authors: Zhang
authors: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Electronic address: wangxudongtj@163.com.
authors: Xudong
authors: X
authors: Wang
authors: Stomatology Hospital of Tianjin Medical University, Tianjin, China. Electronic address: zhudongwangtj@126.com.
authors: Dongwang
authors: D
authors: Zhu
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Electronic address: yangzhihong321@sina.com.
authors: Zhihong
authors: Z
authors: Yang
authors: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Electronic address: zhiqiangqiutianjin@126.com.
authors: Zhiqiang
authors: Z
authors: Qiu
authors: Department of Pathology, Tianjin Hospital, Tianjin, China. Electronic address: banxinchaotj@163.com.
authors: Xinchao
authors: X
authors: Ban
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015820:Cadherins / Q000096:biosynthesis; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D051879:Twist-Related Protein 1 / Q000096:biosynthesis; D014746:Vimentin / Q000096:biosynthesis; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D009687:Nuclear Proteins; D055293:Receptors, Urokinase Plasminogen Activator; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; D000099152:Cadherin 5; C103173:TWIST1 protein, human
keywords: Large-cell lung cancer; Metastasis; Vasculogenic mimicry; uPAR