CD133+ renal progenitor cells contribute to tumor angiogenesis

被引:166
作者
Bruno, Stefania
Bussolati, Benedetta
Grange, Cristina
Collino, Federica
Graziano, Manuela Efrern
Ferrando, Ugo
Camussi, Giovanni
机构
[1] Osped Maggiore S Giovanni Battista, Dipartimento Med Interna, Cattedra Nefrol, Div Urol, I-10126 Turin, Italy
[2] Univ Turin, Dipartimento Med Interna, Turin, Italy
[3] Univ Turin, Ctr Ric Med Sperimentale, Cattedra Nefrol, Turin, Italy
关键词
MESENCHYMAL STEM-CELLS; MARROW-DERIVED CELLS; BONE-MARROW; ENDOTHELIAL-CELLS; HEMATOPOIETIC STEM; IN-VIVO; CANCER; IDENTIFICATION; GROWTH; DIFFERENTIATION;
D O I
10.2353/ajpath.2006.060498
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
In the present study, we tested die hypothesis that resident progenitor cells may contribute to tumor vascularization and growth. CD133(+) cells were isolated from 30 human renal carcinomas and characterized as renal resident progenitor cells on the basis of the expression of renal embryonic and mesenchymal stem cell markers. CD133(+) progenitors differentiated into endothelial and epithelial cells as the normal CD133(+) counterpart present in renal tissue. In the presence of tumor-derived growth factors, these cells were committed to differentiate into endothelial cells able to form vessels in vivo in SCID mice. Undifferentiated CD133(+) progenitors were unable to form tumors when transplanted alone in SCID mice. When co-transplanted with renal carcinoma cells' CD133(+) progenitors significantly enhanced tumor development and growth. This effect was not attributable to the tumorigenic nature of CD133(+) progenitor cells because the same results were obtained with CD133(+) cells from normal kidney. CD133(+) progenitors contributed to tumor vascularization as the majority of neoformed vessels present within the transplanted tumors were of human origin and derived from the co-transplanted CD133(+) progenitors. In conclusion, these results indicate the presence of a renal progenitor cell population in renal carcinomas that may differentiate in endothelial cells and favor vascularization and tumor growth.
引用
收藏
页码:2223 / 2235
页数:13
相关论文
共 57 条
[11]   Role of Pax2 in apoptosis resistance and proinvasive phenotype of Kaposi's sarcoma cells [J].
Buttiglieri, S ;
Deregibus, MC ;
Bravo, S ;
Cassoni, P ;
Chiarle, R ;
Bussolati, B ;
Camussi, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4136-4143
[12]   Adult stem cells in the repair of the injured renal tubule [J].
Cantley, LG .
NATURE CLINICAL PRACTICE NEPHROLOGY, 2005, 1 (01) :22-32
[13]   Prospective identification of tumorigenic prostate cancer stem cells [J].
Collins, AT ;
Berry, PA ;
Hyde, C ;
Stower, MJ ;
Maitland, NJ .
CANCER RESEARCH, 2005, 65 (23) :10946-10951
[14]   Mesoangioblasts - vascular progenitors for extravascular mesodermal tissues [J].
Cossu, G ;
Bianco, P .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2003, 13 (05) :537-542
[15]   Tie2 identifies a hematopoietic monocytes required for tumor lineage of proangiogenic vessel formation and a mesenchymal population of pericyte progenitors [J].
De Palma, M ;
Venneri, MA ;
Galli, R ;
Sergi, LS ;
Politi, LS ;
Sampaolesi, M ;
Naldini, L .
CANCER CELL, 2005, 8 (03) :211-226
[16]   PAX-2 IS A DNA-BINDING PROTEIN EXPRESSED IN EMBRYONIC KIDNEY AND WILMS-TUMOR [J].
DRESSLER, GR ;
DOUGLASS, EC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (04) :1179-1183
[17]   Differential transplantability of tumor-associated stromal cells [J].
Duda, DG ;
Fukumura, D ;
Munn, LL ;
Booth, MF ;
Brown, EB ;
Huang, PG ;
Seed, B ;
Jain, RK .
CANCER RESEARCH, 2004, 64 (17) :5920-5924
[18]   Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer [J].
Florek, M ;
Haase, M ;
Marzesco, AM ;
Freund, D ;
Ehninger, G ;
Huttner, WB ;
Corbeil, D .
CELL AND TISSUE RESEARCH, 2005, 319 (01) :15-26
[19]   ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].
FOLKMAN, J .
NATURE MEDICINE, 1995, 1 (01) :27-31
[20]  
Garton HJL, 1996, ANAT RECORD, V244, P112, DOI 10.1002/(SICI)1097-0185(199601)244:1<112::AID-AR11>3.0.CO