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Titolo:
HOXB7: A key factor for tumor-associated angiogenic switch
Autore:
Care, A; Felicetti, F; Meccia, E; Bottero, L; Parenza, M; Stoppacciaro, A; Peschle, C; Colombo, MP;
Indirizzi:
Ist Super Sanita, Dept Hematol Oncol, I-00161 Rome, Italy Ist Super Sanita Rome Italy I-00161 t Hematol Oncol, I-00161 Rome, Italy Ist Nazl Tumori, Immunotherapy & Gene Therapy Unit, Dept Expt Oncol, I-20133 Milan, Italy Ist Nazl Tumori Milan Italy I-20133 ept Expt Oncol, I-20133 Milan, Italy Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00100 Rome, Italy Univ Roma La Sapienza Rome Italy I-00100 d & Pathol, I-00100 Rome, Italy
Titolo Testata:
CANCER RESEARCH
fascicolo: 17, volume: 61, anno: 2001,
pagine: 6532 - 6539
SICI:
0008-5472(20010901)61:17<6532:HAKFFT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR TYROSINE KINASES; BLOOD-VESSEL FORMATION; GROWTH-FACTOR VEGF; CELL-PROLIFERATION; HOMEOBOX GENES; MELANOMA-CELLS; EXPRESSION; CANCER; ANGIOPOIETIN-1; TUMORIGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Care, A Ist Super Sanita, Dept Hematol Oncol, Viale Regina Elena 299, I-00161 Rome, Italy Ist Super Sanita Viale Regina Elena 299 Rome Italy I-00161 Italy
Citazione:
A. Care et al., "HOXB7: A key factor for tumor-associated angiogenic switch", CANCER RES, 61(17), 2001, pp. 6532-6539

Abstract

We had demonstrated previously a functional bridge between altered homebox(HOX) gene expression and tumor progression through HOXB7 transactivation of basic fibroblast growth factor. Here, we have studied whether HOXB7, in addition to basic fibroblast growth factor, may induce other genes directly or indirectly related to neoangiogenesis and tumor invasion. Parental, beta -galactosidase-transduced, and HOXB7-transduced SkBr3 cell lines were examined for the expression of several growth factors and growth factor receptors involved in the proliferative and angiogenic processes. Vascular endothelial growth factor, melanoma growth-stimulatory activity/growth-related oncogenene alpha, interleukin-8, andangiopoietin-2 were up-regulated by HOXB7 transduction. The exception was angiopoietin-1 expression that was abrogated. Additional analyses included the expression levels of enzymes such as matrix metalloprotease (MMP)-2 andMMP-9 and heparanase, capable of proteolytic degradation of extracellular matrix and basement membranes. Results showed an induction of only MMP-9. The functional implication of such a finding was tested using an in vitro coculture assay in a three-dimensional matrix. A delay of differentiation with persistent nests of proliferating cells was found in endothelial cells cocultured with HOXB7-transduced SkBr3 cells. Tumorigenicity of these cellshas been evaluated in vivo. Xenograft into athymic nude mice showed that SkBr3/HOXB7 cells developed tumors in mice, either irradiated or not, whereas parental SkBr3 cells did not show any tumor take unless mice were sublethally irradiated. Comparison of tumor nodules for vascularization by CD-31 and CD-34 immunostaining revealed an increased number of blood vessels in tumors expressing HOXB7. Together, the results indicate HOXB7 as a key factorup-regulating a variety of proangiogenic stimuli. Thus, HOXB7 gene or protein is a target to aim at to inhibit tumor-associated neoangiogenesis, considering the number and the redundancy of proangiogenic molecules that should be targeted one by one to theoretically achieve the same effect.

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Documento generato il 05/07/20 alle ore 07:13:32