Target Validation Information
Target ID T50444
Target Name Connective tissue growth factor
Target Type
Clinical Trial
Action against Disease Model FG-3019 Administration of a neutralizing CTGF-specific monoclonal antibody, FG-3019, had no effect on monolayer cell proliferation, but blocked AIG in soft agar. Consistent with this observation, anti-CTGF treatment of mice bearing established CTGF-expressing t uMors abrogated CTGF-dependent t uMor growth and inhibited lymph node metastases without any toxicity observed in normal tissue. [552604] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Connective tissue growth factor (CTGF) is a mediator of growth factor activity, and Ctgf knockouts die at birth from respiratory failure due to skeletal dysplasia. Previous microarray analysis revealed Ctgf down-regulation in the hypoplastic lungs of amyogenic mouse embryos. This study, therefore, examined pulmonary development in Ctgf-/- mouse fetuses to investigate if respiration could also have been impaired by lung abnormalities. The Ctgf-/- lungs were hypoplastic, with reduced cell proliferation and increased apoptosis. PDGF-B, its receptor and IGF-I, were markedly attenuated and the TTF-1 gradient lost. Type II pne uMocyte differentiation was perturbed, the cells depicting excessive glycogen retention and diminished lamellar body and nuclear size, though able to synthesize surfactant-associated protein. However, type I pne uMocyte differentiation was not affected by Ctgf deletion. Our findings indicate that the absence of Ctgf and/or its protein product, CTGF, may induce pulmonary hypoplasia by both disrupting basic lung developmental processes and restricting thoracic expansion. [552604]
References
Ref 552604Connective tissue growth factor-specific monoclonal antibody therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 2006 Jun 1;66(11):5816-27.

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