title: CTGF is a therapeutic target for metastatic melanoma.
abstract: Metastatic melanoma remains a devastating disease with a 5-year survival rate of less than five percent. Despite recent advances in targeted therapies for melanoma, only a small percentage of melanoma patients experience durable remissions. Therefore, it is critical to identify new therapies for the treatment of advanced melanoma. Here, we define connective tissue growth factor (CTGF) as a therapeutic target for metastatic melanoma. Clinically, CTGF expression correlates with tumor progression and is strongly induced by hypoxia through HIF-1 and HIF-2-dependent mechanisms. Genetic inhibition of CTGF in human melanoma cells is sufficient to significantly reduce orthotopic tumor growth, as well as metastatic tumor growth in the lung of severe combined immunodeficient (SCID) mice. Mechanistically, inhibition of CTGF decreased invasion and migration associated with reduced matrix metalloproteinase-9 expression. Most importantly, the anti-CTGF antibody, FG-3019, had a profound inhibitory effect on the progression of established metastatic melanoma. These results offer the first preclinical validation of anti-CTGF therapy for the treatment of advanced melanoma and underscore the importance of tumor hypoxia in melanoma progression.
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: E C
authors: EC
authors: Finger
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: C-F
authors: CF
authors: Cheng
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: T R
authors: TR
authors: Williams
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: E B
authors: EB
authors: Rankin
authors: Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors: B
authors: B
authors: Bedogni
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: L
authors: L
authors: Tachiki
authors: FibroGen Inc., San Francisco, CA, USA.
authors: S
authors: S
authors: Spong
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: A J
authors: AJ
authors: Giaccia
authors: Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors: M B
authors: MB
authors: Powell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D051792:Basic Helix-Loop-Helix Proteins; D055513:Connective Tissue Growth Factor; D051793:Hypoxia-Inducible Factor 1; D020780:Matrix Metalloproteinase 9; D000099162:Endothelial PAS Domain-Containing Protein 1; C526317:CCN2 protein, human; C560078:pamrevlumab