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- W136337072 abstract "4150 Background: Connective Tissue Growth Factor (CTGF) is a member of the CCN family of cysteine- rich secreted glycoproteins and is a novel factor recently implicated in tumor progression of several distinct tumor cell types. Elevated CTGF expression levels are correlated with tumor stage and poor prognosis in humans and CTGF expression is elevated in human pancreatic adenocarcinomas and some pancreatic cancer cell lines. Methods: To directly address the role of CTGF in pancreatic cancer, we generated pancreatic tumor cell lines that over-express different levels of human CTGF. The effect of CTGF over-expression or inhibition of CTGF with a human monoclonal antibody, on cell proliferation was measured in vitro in monolayer cultures or soft agar assays and in vivo in tumor xenograft studies. Results: CTGF over-expression did not enhance proliferation of cells plated on plastic in two-dimensional cultures but in contrast, markedly enhanced the ability of cells to proliferate in anchorage-independent growth (AIG) assays when cells were plated in soft agar. Consistent with this finding, a neutralizing monoclonal antibody (mAb) specific for CTGF blocked anchorage-independent growth but had no effect on anchorage-dependent cell proliferation. The capacity of CTGF to enhance AIG in vitro led to enhanced tumor growth in vivo when these cells were implanted sub-cutaneously in standard xenograft models. Thus, compared to vector control transfectants that do not express CTGF, CTGF over-expressing cells exhibited enhanced tumor growth where tumor size correlated with CTGF over-expression in vitro. Elevated CTGF expression levels also correlated with increased mortality. Administration of a CTGF-specific mAb to mice with established CTGF expressing tumors abrogated CTGF-dependent tumor growth. A preliminary analysis of circulating CTGF levels in human pancreatic cancer patients indicates higher levels of CTGF as compared to normal subjects. Conclusions: Together these studies implicate CTGF as a novel target in pancreatic cancer and suggest that inhibition of CTGF with a human monoclonal antibody may be a promising new therapy for this disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration FibroGen FibroGen FibroGen" @default.
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- W136337072 date "2005-06-01" @default.
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- W136337072 title "Inhibition of pancreatic tumor growth and progression by a human monoclonal antibody specific for connective tissue growth factor" @default.
- W136337072 doi "https://doi.org/10.1200/jco.2005.23.16_suppl.4150" @default.
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