Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer

Takuma Aikawa, Jason Gunn, Suzanne M. Spong, Stephen J. Klaus, Murray Korc

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Connective tissue growth factor (CTGF) plays an important role in fibrosis by modulating cell migration and cell growth but may also modify tumor growth and metastasis. Because CTGF is overexpressed in pancreatic ductal adenocarcinoma, we investigated the in vitro effects of CTGF on the proliferation and invasiveness of PANC-1 pancreatic cancer cells and examined the consequences of its in vivo inhibition on the growth and metastasis of these cells using a fully human CTGF-specific monoclonal antibody (FG-3019) in an orthotopic nude mouse model. Although PANC-1 cells expressed relatively high levels of endogenous CTGF mRNA, the addition of CTGF to conditioned medium increased the proliferation and invasiveness of PANC-1 cells. Moreover, transforming growth factor-β1 caused a further increase in CTGF expression in these cells. In vivo, the twice weekly i.p. administration of FG-3019 decreased tumor growth and metastasis and attenuated tumor angiogenesis and cancer cell proliferation. FG-3019 did not enhance apoptosis and did not attenuate the inhibitory effects of gemcitabine on tumor growth and metastasis. These findings suggest that CTGF may contribute to aberrant autocrine and paracrine pathways that promote pancreatic cancer cell growth, invasion, metastasis, and angiogenesis. Therefore, blocking CTGF actions with FG-3019 may represent a novel therapeutic approach in pancreatic ductal adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)1108-1116
Number of pages9
JournalMolecular Cancer Therapeutics
Volume5
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

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Neoplasm Antibodies
Connective Tissue Growth Factor
Pancreatic Neoplasms
Neoplasm Metastasis
Growth
Neoplasms
gemcitabine
Adenocarcinoma
Transforming Growth Factors
Conditioned Culture Medium
Nude Mice
Cell Movement
Fibrosis
Monoclonal Antibodies
Cell Proliferation
Apoptosis
Messenger RNA
FG 3019

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. / Aikawa, Takuma; Gunn, Jason; Spong, Suzanne M.; Klaus, Stephen J.; Korc, Murray.

In: Molecular Cancer Therapeutics, Vol. 5, No. 5, 05.2006, p. 1108-1116.

Research output: Contribution to journalArticle

Aikawa, Takuma ; Gunn, Jason ; Spong, Suzanne M. ; Klaus, Stephen J. ; Korc, Murray. / Connective tissue growth factor-specific antibody attenuates tumor growth, metastasis, and angiogenesis in an orthotopic mouse model of pancreatic cancer. In: Molecular Cancer Therapeutics. 2006 ; Vol. 5, No. 5. pp. 1108-1116.
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