Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer.

作者: Hanseul Yang , Chan Kim , Min-Ju Kim , Reto A Schwendener , Kari Alitalo

DOI: 10.1186/1476-4598-10-36

关键词:

摘要: Most bladder cancer patients experience lymphatic metastasis in the course of disease progression, yet relationship between lymphangiogenesis and is not well known. The aim this study to elucidate underlying mechanisms how expanded vessels tumor microenvironment interacts each other find effective therapeutic options inhibit metastasis. orthotopic urinary (OUBC) model was generated by intravesical injection MBT-2 cell lines. We investigated angiogenesis, lymphangiogenesis, CD11b+/CD68+ tumor-associated macrophages (TAM) using immunofluorescence staining. OUBC displayed a profound massive infiltration TAM primary lymph nodes. flocked near express higher levels VEGF-C/D than CD11b- cells. Because VEGFR-3 highly expressed vascular endothelial cells, could assist paracrine manner tumor. expressing adenovirus administered block signaling pathway clodronate liposome used deplete TAM. blockade with soluble VEGF receptor-3 markedly inhibited OUBC. In addition, depletion exerted similar effects on are main factors cancer. Moreover, plays an important role these processes producing VEGF-C/D. inhibition provide another target recurrence invasive

参考文章(37)
B. H. Bochner, R. J. Cote, N. Weidner, S. Groshen, S.-C. Chen, D. G. Skinner, P. W. Nichols, Angiogenesis in Bladder Cancer: Relationship Between Microvessel Density and Tumor Prognosis Journal of the National Cancer Institute. ,vol. 87, pp. 1603- 1612 ,(1995) , 10.1093/JNCI/87.21.1603
Takashi Karashima, Randall Millikan, Paul Sweeney, Keiji Inoue, Colin P. N. Dinney, Taro Shuin, Chiaki Yoshikawa, Joel W. Slaton, The prognostic value of angiogenesis factor expression for predicting recurrence and metastasis of bladder cancer after neoadjuvant chemotherapy and radical cystectomy. Clinical Cancer Research. ,vol. 6, pp. 4866- 4873 ,(2000)
Chung-Hyun Cho, Young Jun Koh, Jinah Han, Hoon-Ki Sung, Hyuek Jong Lee, Tohru Morisada, Reto A. Schwendener, Rolf A. Brekken, Guson Kang, Yuichi Oike, Tae-Saeng Choi, Toshio Suda, Ook-Joon Yoo, Gou Young Koh, Angiogenic Role of LYVE-1-positive Macrophages in Adipose Tissue Circulation Research. ,vol. 100, ,(2007) , 10.1161/01.RES.0000259564.92792.93
Chrystelle Lamagna, Michel Aurrand-Lions, Beat A. Imhof, Dual role of macrophages in tumor growth and angiogenesis Journal of Leukocyte Biology. ,vol. 80, pp. 705- 713 ,(2006) , 10.1189/JLB.1105656
JianMin Lin, Alshad S. Lalani, Thomas C. Harding, Melissa Gonzalez, Wei-Wei Wu, Bo Luan, Guang Huan Tu, Kathryn Koprivnikar, Melinda J. VanRoey, Yulong He, Kari Alitalo, Karin Jooss, Inhibition of Lymphogenous Metastasis Using Adeno-Associated Virus-Mediated Gene Transfer of a Soluble VEGFR-3 Decoy Receptor Cancer Research. ,vol. 65, pp. 6901- 6909 ,(2005) , 10.1158/0008-5472.CAN-05-0408
Sebastian F. Schoppmann, Peter Birner, Johannes Stöckl, Romana Kalt, Robert Ullrich, Carola Caucig, Ernst Kriehuber, Katalin Nagy, Kari Alitalo, Dontscho Kerjaschki, Tumor-Associated Macrophages Express Lymphatic Endothelial Growth Factors and Are Related to Peritumoral Lymphangiogenesis American Journal of Pathology. ,vol. 161, pp. 947- 956 ,(2002) , 10.1016/S0002-9440(10)64255-1
Aude Flechon, Jean-Pierre Droz, Chemotherapy practices and perspectives in invasive bladder cancer. Expert Review of Anticancer Therapy. ,vol. 6, pp. 1473- 1482 ,(2006) , 10.1586/14737140.6.10.1473
Taija Mäkinen, Lotta Jussila, Tanja Veikkola, Terhi Karpanen, Mikko I. Kettunen, Kalevi J. Pulkkanen, Risto Kauppinen, David G. Jackson, Hajime Kubo, Shin-Ichi Nishikawa, Seppo Ylä-Herttuala, Kari Alitalo, Inhibition of lymphangiogenesis with resulting lymphedema in transgenic mice expressing soluble VEGF receptor-3 Nature Medicine. ,vol. 7, pp. 199- 205 ,(2001) , 10.1038/84651
Marcia R Saban, Rheal Towner, Nataliya Smith, Andrew Abbott, Michal Neeman, Carole A Davis, Cindy Simpson, Julie Maier, Sylvie Mémet, Xue-Ru Wu, Ricardo Saban, Lymphatic vessel density and function in experimental bladder cancer BMC Cancer. ,vol. 7, pp. 219- 219 ,(2007) , 10.1186/1471-2407-7-219