Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

Autor: Brian S. Gloss, David K. Chang, Michael J. Birrer, Samuel Yuen, Carol Wong, Viive M. Howell, Rajmohan Murali, Goli Samimi, Suzanne M. Spong, Laura M. Brown, Neville F. Hacker, Marc D. Jones, Samuel C. Mok, Emily K. Colvin, Sue Ghosh, Christopher J. Scarlett, Kim Moran-Jones
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Pathology
endocrine system diseases
Metastasis
Ovarian tumor
Cell Movement
Databases
Genetic
Molecular Targeted Therapy
Peritoneal Neoplasms
Aged
80 and over
Ovarian Neoplasms
integumentary system
Antibodies
Monoclonal
Middle Aged
female genital diseases and pregnancy complications
3. Good health
Up-Regulation
Serous fluid
ovarian cancer
Oncology
Female
Research Paper
Signal Transduction
Adult
medicine.medical_specialty
Stromal cell
Antineoplastic Agents
Antibodies
Monoclonal
Humanized
Cell Line
Tumor
medicine
Biomarkers
Tumor
Cell Adhesion
metastasis
tumor microenvironment
Humans
Neoplasm Invasiveness
Aged
Tumor microenvironment
business.industry
Gene Expression Profiling
Connective Tissue Growth Factor
CTGF
FG-3019
medicine.disease
Tumor progression
Neoplasm Grading
Stromal Cells
Ovarian cancer
business
Neoplasms
Cystic
Mucinous
and Serous
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.
Databáze: OpenAIRE
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