Hedgehog Signaling Activation in Hepatic Stellate Cells Promotes Angiogenesis and Vascular Mimicry in Hepatocellular Carcinoma

被引：37

作者：

Li, Wei ^{[1
]}

Miao, Shuanlin ^{[1
]}

Miao, Manyuan ^{[1
]}

Li, Renshuan ^{[1
]}

Cao, Xiaopeng ^{[1
]}

Zhang, Kun ^{[1
]}

Huang, Genzuan ^{[1
]}

Fu, Bin ^{[1
]}

机构：

[1] Yanan Univ, Dept Surg Oncol, Xianyang Hosp, 38 Wenlin Rd, Xianyang, Shannxi, Peoples R China

来源：

CANCER INVESTIGATION | 2016年 / 34卷 / 09期

关键词：

Hepatocellular carcinoma; Hepatic stellate cells; Hedgehog signaling; Angiogenesis; Vascular mimicry; VASCULOGENIC MIMICRY; PANCREATIC-CANCER; EXPRESSION; PATHWAY; MATRIX; HEPATOCARCINOGENESIS; MECHANISMS; SORAFENIB;

D O I：

10.1080/07357907.2016.1227442

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Previous studies have established that hedgehog (Hh) signaling mediates tumor-stroma interaction and promotes hepatocellular carcinoma progression. Here, we demonstrated that activation of Hh signaling in hepatic stellate cell (HSC) line LX-2 by Huh-7-derived sonic Hh led to increased secretion of angiogenic factors and promoted angiogenesis in vitro. The activated LX-2 also enhanced vascular mimicry of hepatoma cells. Furthermore, co-injection of Huh-7 and LX-2 significantly accelerated tumor growth with enhanced angiogenesis compared with Huh-7 alone, which could be partly abrogated by Hh signaling inhibitor. Collectively, our data showed that paracrine Hh signaling mediated pro-angiogenic function of HSC and enhanced hepatoma growth.

引用

收藏

页码：424 / 430

页数：7

相关论文

共 30 条

[1]

Phase II study of sorafenib in patients with advanced hepatocellular carcinoma [J].

Abou-Alfa, Ghassan K. ;

Schwartz, Lawrence ;

Ricci, Sergio ;

Amadori, Dino ;

Santoro, Armando ;

Figer, Arie ;

De Greve, Jacques ;

Douillard, Jean-Yves ;

Lathia, Chetan ;

Schwartz, Brian ;

Taylor, Ian ;

Moscovici, Marius ;

Saltz, Leonard B. .

JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (26) :4293-4300

[2]

Differential Expression of Sonic Hedgehog Protein in Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma [J].

Al-Bahrani, Redha ;

Nagamori, Seishi ;

Leng, Roger ;

Petryk, Anna ;

Sergi, Consolato .

PATHOLOGY & ONCOLOGY RESEARCH, 2015, 21 (04) :901-908

[3]

Hedgehog Signaling Blockade Delays Hepatocarcinogenesis Induced by Hepatitis B Virus X Protein [J].

Arzumanyan, Alla ;

Sambandam, Vaishnavi ;

Clayton, Marcia M. ;

Choi, Steve S. ;

Xie, Guanhua ;

Diehl, Anna Mae ;

Yu, Dae-Yeul ;

Feitelson, Mark A. .

CANCER RESEARCH, 2012, 72 (22) :5912-5920

[4]

Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system [J].

Augustin, Hellmut G. ;

Koh, Gou Young ;

Thurston, Gavin ;

Alitalo, Kari .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (03) :165-177

[5]

Hepatic stellate cells and extracellular matrix in hepatocellular carcinoma: more complicated than ever [J].

Carloni, Vinicio ;

Tu Vinh Luong ;

Rombouts, Krista .

LIVER INTERNATIONAL, 2014, 34 (06) :834-843

[6]

Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma [J].

Chan, Isaac S. ;

Guy, Cynthia D. ;

Chen, Yuping ;

Lu, Jiuyi ;

Swiderska-Syn, Marzena ;

Michelotti, Gregory A. ;

Karaca, Gamze ;

Xie, Guanhua ;

Krueger, Leandi ;

Syn, Wing-Kin ;

Anderson, Blair R. ;

Pereira, Thiago A. ;

Choi, Steve S. ;

Baldwin, Albert S. ;

Diehl, Anna Mae .

CANCER RESEARCH, 2012, 72 (24) :6344-6350

[7]

Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells [J].

Chen, Weiwei ;

Tang, Tracy ;

Eastham-Anderson, Jeff ;

Dunlap, Debra ;

Alicke, Bruno ;

Nannini, Michelle ;

Gould, Stephen ;

Yauch, Robert ;

Modrusan, Zora ;

DuPree, Kelly J. ;

Darbonne, Walter C. ;

Plowman, Greg ;

de Sauvage, Frederic J. ;

Callahan, Christopher A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (23) :9589-9594

[8]

Hepatic expression of Sonic Hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model [J].

Chung, Sook In ;

Moon, Hyuk ;

Ju, Hye-Lim ;

Cho, Kyung Joo ;

Kim, Do Young ;

Han, Kwang-Hyub ;

Eun, Jung Woo ;

Nam, Suk Woo ;

Ribback, Silvia ;

Dombrowski, Frank ;

Calvisi, Diego F. ;

Ro, Simon Weonsang .

JOURNAL OF HEPATOLOGY, 2016, 64 (03) :618-627

[9]

Stellate cells and the development of liver cancer: Therapeutic potential of targeting the stroma [J].

Coulouarn, Cedric ;

Clement, Bruno .

JOURNAL OF HEPATOLOGY, 2014, 60 (06) :1306-1309

[10]

Inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma [J].

Han, Ke-Qi ;

He, Xue-Qun ;

Ma, Meng-Yu ;

Guo, Xiao-Dong ;

Zhang, Xue-Min ;

Chen, Jie ;

Han, Hui ;

Zhang, Wei-Wei ;

Zhu, Quan-Gang ;

Nian, Hua ;

Ma, Li-Jun .

WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (16) :4864-4874