Inhibition of connective tissue growth factor (CTGF/CCN2) expression decreases the survival and myogenic differentiation of human rhabdomyosarcoma cells.
Connective tissue growth factor (CTGF/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microarray screen of genes expressed by human rhabdomyosarcoma cells. Rhabdomyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomyosarcoma. Human rhabdomyosarcoma cells of the embryonal (RD/12, RD/18, CCA) and the alveolar histotype (RMZ-RC2, SJ-RH4, SJ-RH30), rhabdomyosarcoma tumor specimens, and normal skeletal muscle cells expressed CTGF. To determine the function of CTGF, we treated rhabdomyosarcoma cells with a CTGF antisense oligonucleotide or with a CTGF small interfering RNA (siRNA). Both treatments inhibited rhabdomyosarcoma cell growth, suggesting the existence of a new autocrine loop based on CTGF. CTGF antisense oligonucleotide-mediated growth inhibition was specifically due to a significant increase in apoptosis, whereas cell proliferation was unchanged. CTGF antisense oligonucleotide induced a strong decrease in the level of myogenic differentiation of rhabdomyosarcoma cells, whereas the addition of recombinant CTGF significantly increased the proportion of myosin-positive cells. CTGF emerges as a survival and differentiation factor and could be a new therapeutic target in human rhabdomyosarcoma.
Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna, Italy.
Stefania
S
Croci
Lorena
L
Landuzzi
Annalisa
A
Astolfi
Giordano
G
Nicoletti
Angelo
A
Rosolen
Francesca
F
Sartori
Matilde Y
MY
Follo
Noelynn
N
Oliver
Carla
C
De Giovanni
Patrizia
P
Nanni
Pier-Luigi
PL
Lollini
D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D055513:Connective Tissue Growth Factor; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology*; D055514:Nephroblastoma Overexpressed Protein; D012208:Rhabdomyosarcoma / Q000473:pathology*
C526317:CCN2 protein, human; C526319:CCN3 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D055514:Nephroblastoma Overexpressed Protein; D055513:Connective Tissue Growth Factor