Targeting of insulin-like growth factor-I receptor with a monoclonal antibody inhibits growth of hepatic metastases from human colon carcinoma in mice

Todd W. Bauer, Fan Fan, Wenbiao Liu, Ernest R. Camp, Anthony Yang, Ray J. Somcio, Corazon D. Bucana, Rajeeva Singh, Lee M. Ellis

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Colorectal carcinomas (CRC) express high levels of insulin-like growth factor-I/II (IGF-I/II) and the receptor (IGF-IR). We hypothesized that selective inhibition of IGF-IR would inhibit hepatic growth of human CRC in mice. Methods: Human CRC cells were treated in vitro with anti-IGF-IR monoclonal antibody (MoAB) with and without oxaliplatin to assess cytotoxicity. The effect of anti-IGF-IR MoAB on IGF-I-induced vascular endothelial growth factor (VEGF) production in human CRC cells was assessed by Northern blot and ELISA. We injected human CRC cells intrahepatically in nude mice, and then administered anti-IGF-IR MoAB with and without oxaliplatin. We delayed treatment in one group until large hepatic tumors were present. We assessed tumors for apoptosis, proliferation, and angiogenesis. Results: Anti-IGF-IR MoAB and oxaliplatin inhibited CRC cell growth in vitro and combination treatment was even more effective. IGF-I stimulation of CRC cells resulted in significant upregulation of VEGF and this was completely inhibited by pretreatment with anti-IGF-IR MoAB. Anti-IGF-IR MoAB significantly inhibited hepatic growth of tumors in mice. Anti-IGF-IR MoAB plus oxaliplatin led to a significantly greater inhibition of tumor growth. Anti-IGF-IR MoAB plus oxaliplatin was just as effective at inhibiting growth of larger, more advanced liver tumors. Anti-IGF-IR MoAB, alone and in combination with oxaliplatin, led to a significant increase in tumor cell apoptosis, and a significant inhibition of tumor cell proliferation and angiogenesis. Conclusions: These findings suggest that IGF-IR is a potential target for therapy in patients with advanced CRC.

Original languageEnglish (US)
Pages (from-to)2838-2846
Number of pages9
JournalAnnals of Surgical Oncology
Volume14
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

IGF Type 2 Receptor
IGF Type 1 Receptor
oxaliplatin
Colon
Monoclonal Antibodies
Neoplasm Metastasis
Carcinoma
Colorectal Neoplasms
Liver
Growth
Neoplasms
Insulin-Like Growth Factor I
Vascular Endothelial Growth Factor A
Apoptosis
Nude Mice
Northern Blotting

Keywords

  • Colon carcinoma
  • IGF-I
  • Liver metastasis
  • Oxaliplatin

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Targeting of insulin-like growth factor-I receptor with a monoclonal antibody inhibits growth of hepatic metastases from human colon carcinoma in mice. / Bauer, Todd W.; Fan, Fan; Liu, Wenbiao; Camp, Ernest R.; Yang, Anthony; Somcio, Ray J.; Bucana, Corazon D.; Singh, Rajeeva; Ellis, Lee M.

In: Annals of Surgical Oncology, Vol. 14, No. 10, 10.2007, p. 2838-2846.

Research output: Contribution to journalArticle

Bauer, Todd W. ; Fan, Fan ; Liu, Wenbiao ; Camp, Ernest R. ; Yang, Anthony ; Somcio, Ray J. ; Bucana, Corazon D. ; Singh, Rajeeva ; Ellis, Lee M. / Targeting of insulin-like growth factor-I receptor with a monoclonal antibody inhibits growth of hepatic metastases from human colon carcinoma in mice. In: Annals of Surgical Oncology. 2007 ; Vol. 14, No. 10. pp. 2838-2846.
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abstract = "Background: Colorectal carcinomas (CRC) express high levels of insulin-like growth factor-I/II (IGF-I/II) and the receptor (IGF-IR). We hypothesized that selective inhibition of IGF-IR would inhibit hepatic growth of human CRC in mice. Methods: Human CRC cells were treated in vitro with anti-IGF-IR monoclonal antibody (MoAB) with and without oxaliplatin to assess cytotoxicity. The effect of anti-IGF-IR MoAB on IGF-I-induced vascular endothelial growth factor (VEGF) production in human CRC cells was assessed by Northern blot and ELISA. We injected human CRC cells intrahepatically in nude mice, and then administered anti-IGF-IR MoAB with and without oxaliplatin. We delayed treatment in one group until large hepatic tumors were present. We assessed tumors for apoptosis, proliferation, and angiogenesis. Results: Anti-IGF-IR MoAB and oxaliplatin inhibited CRC cell growth in vitro and combination treatment was even more effective. IGF-I stimulation of CRC cells resulted in significant upregulation of VEGF and this was completely inhibited by pretreatment with anti-IGF-IR MoAB. Anti-IGF-IR MoAB significantly inhibited hepatic growth of tumors in mice. Anti-IGF-IR MoAB plus oxaliplatin led to a significantly greater inhibition of tumor growth. Anti-IGF-IR MoAB plus oxaliplatin was just as effective at inhibiting growth of larger, more advanced liver tumors. Anti-IGF-IR MoAB, alone and in combination with oxaliplatin, led to a significant increase in tumor cell apoptosis, and a significant inhibition of tumor cell proliferation and angiogenesis. Conclusions: These findings suggest that IGF-IR is a potential target for therapy in patients with advanced CRC.",
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T1 - Targeting of insulin-like growth factor-I receptor with a monoclonal antibody inhibits growth of hepatic metastases from human colon carcinoma in mice

AU - Bauer, Todd W.

AU - Fan, Fan

AU - Liu, Wenbiao

AU - Camp, Ernest R.

AU - Yang, Anthony

AU - Somcio, Ray J.

AU - Bucana, Corazon D.

AU - Singh, Rajeeva

AU - Ellis, Lee M.

PY - 2007/10

Y1 - 2007/10

N2 - Background: Colorectal carcinomas (CRC) express high levels of insulin-like growth factor-I/II (IGF-I/II) and the receptor (IGF-IR). We hypothesized that selective inhibition of IGF-IR would inhibit hepatic growth of human CRC in mice. Methods: Human CRC cells were treated in vitro with anti-IGF-IR monoclonal antibody (MoAB) with and without oxaliplatin to assess cytotoxicity. The effect of anti-IGF-IR MoAB on IGF-I-induced vascular endothelial growth factor (VEGF) production in human CRC cells was assessed by Northern blot and ELISA. We injected human CRC cells intrahepatically in nude mice, and then administered anti-IGF-IR MoAB with and without oxaliplatin. We delayed treatment in one group until large hepatic tumors were present. We assessed tumors for apoptosis, proliferation, and angiogenesis. Results: Anti-IGF-IR MoAB and oxaliplatin inhibited CRC cell growth in vitro and combination treatment was even more effective. IGF-I stimulation of CRC cells resulted in significant upregulation of VEGF and this was completely inhibited by pretreatment with anti-IGF-IR MoAB. Anti-IGF-IR MoAB significantly inhibited hepatic growth of tumors in mice. Anti-IGF-IR MoAB plus oxaliplatin led to a significantly greater inhibition of tumor growth. Anti-IGF-IR MoAB plus oxaliplatin was just as effective at inhibiting growth of larger, more advanced liver tumors. Anti-IGF-IR MoAB, alone and in combination with oxaliplatin, led to a significant increase in tumor cell apoptosis, and a significant inhibition of tumor cell proliferation and angiogenesis. Conclusions: These findings suggest that IGF-IR is a potential target for therapy in patients with advanced CRC.

AB - Background: Colorectal carcinomas (CRC) express high levels of insulin-like growth factor-I/II (IGF-I/II) and the receptor (IGF-IR). We hypothesized that selective inhibition of IGF-IR would inhibit hepatic growth of human CRC in mice. Methods: Human CRC cells were treated in vitro with anti-IGF-IR monoclonal antibody (MoAB) with and without oxaliplatin to assess cytotoxicity. The effect of anti-IGF-IR MoAB on IGF-I-induced vascular endothelial growth factor (VEGF) production in human CRC cells was assessed by Northern blot and ELISA. We injected human CRC cells intrahepatically in nude mice, and then administered anti-IGF-IR MoAB with and without oxaliplatin. We delayed treatment in one group until large hepatic tumors were present. We assessed tumors for apoptosis, proliferation, and angiogenesis. Results: Anti-IGF-IR MoAB and oxaliplatin inhibited CRC cell growth in vitro and combination treatment was even more effective. IGF-I stimulation of CRC cells resulted in significant upregulation of VEGF and this was completely inhibited by pretreatment with anti-IGF-IR MoAB. Anti-IGF-IR MoAB significantly inhibited hepatic growth of tumors in mice. Anti-IGF-IR MoAB plus oxaliplatin led to a significantly greater inhibition of tumor growth. Anti-IGF-IR MoAB plus oxaliplatin was just as effective at inhibiting growth of larger, more advanced liver tumors. Anti-IGF-IR MoAB, alone and in combination with oxaliplatin, led to a significant increase in tumor cell apoptosis, and a significant inhibition of tumor cell proliferation and angiogenesis. Conclusions: These findings suggest that IGF-IR is a potential target for therapy in patients with advanced CRC.

KW - Colon carcinoma

KW - IGF-I

KW - Liver metastasis

KW - Oxaliplatin

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U2 - 10.1245/s10434-007-9486-5

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