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Screening and Identification of Small Peptides Targeting Fibroblast Growth Factor Receptor2 using a Phage Display Peptide Library
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Fibroblast growth factor receptor 2 IIIc as a therapeutic target for colorectal cancer cells

Yoko Matsuda1, Masahito Hagio, Tomoko Seya

  • 1Department of Pathology and Integrative Oncological Pathology, Nippon Medical School, Tokyo, Japan. ishiwata@nms.ac.jp

Molecular Cancer Therapeutics
|July 11, 2012
PubMed

Insights

Fibroblast growth factor receptor 2 variant IIIc (FGFR2IIIc) promotes colorectal cancer growth and metastasis. Targeting FGFR2IIIc with monoclonal antibodies shows promise for effective colorectal carcinoma therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Colorectal carcinomas frequently overexpress growth factors and receptors like FGF and FGFR.
  • FGFR2 overexpression is linked to metastasis, while its isoforms FGFR2IIIb and FGFR2IIIc have distinct roles in cancer progression.

Purpose of the Study:

  • To investigate the expression and function of the FGFR2IIIc isoform in colorectal carcinoma.
  • To evaluate the therapeutic potential of targeting FGFR2IIIc in colorectal cancer.

Main Methods:

  • Immunohistochemistry to detect FGFR2IIIc expression in normal and cancerous colorectal tissues.
  • In vitro studies using transfected colorectal carcinoma cells to assess FGFR2IIIc's impact on cell behavior.
  • In vivo tumor formation studies in nude mice.
  • Treatment of cancer cells with anti-FGFR2IIIc monoclonal antibody.

Main Results:

  • FGFR2IIIc expression increases progressively from hyperplastic polyps to carcinomas.
  • FGFR2IIIc expression in 27% of colorectal carcinomas correlated with distant metastasis and poor prognosis.
  • FGFR2IIIc promoted cell growth, migration, invasion, and tumor formation while reducing cell adhesion.
  • Anti-FGFR2IIIc antibody inhibited tumor growth and migration.

Conclusions:

  • FGFR2IIIc is a significant factor in colorectal carcinogenesis and tumor progression.
  • Targeting FGFR2IIIc with monoclonal antibodies presents a promising therapeutic strategy for colorectal carcinoma.

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