Metabolic syndrome and colorectal cancer

Is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process?

Jane Jijun Liu, Mihaela Druta, David Shibata, Domenico Coppola, Ivette Boler, Abul Elahi, Richard R. Reich, Erin Siegel, Martine Extermann

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. Materials and Methods: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6. months after surgery. Results: The MS group had significantly higher baseline and post-operative fasting insulin levels (p. <. 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p. <. 0.001) while IR expression showed no difference. Interestingly, 64% of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumor IGF-1R over-expression (80%) was confirmed, but there was no difference between MS and non-MS patients. Tumor RAGE over-expression was found in 67% of patients and was equally distributed between the two groups. Conclusions: Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalJournal of Geriatric Oncology
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Insulin Receptor
Hyperinsulinism
Colorectal Neoplasms
Somatomedins
Neoplasms
IGF Type 1 Receptor
Vascular Endothelial Growth Factor A
Interleukin-6
Fasting
Insulin
Somatomedin Receptors
Microvessels
Reverse Transcription
Immunohistochemistry
Polymerase Chain Reaction
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Geriatrics and Gerontology

Cite this

Metabolic syndrome and colorectal cancer : Is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process? / Liu, Jane Jijun; Druta, Mihaela; Shibata, David; Coppola, Domenico; Boler, Ivette; Elahi, Abul; Reich, Richard R.; Siegel, Erin; Extermann, Martine.

In: Journal of Geriatric Oncology, Vol. 5, No. 1, 01.01.2014, p. 40-48.

Research output: Contribution to journalArticle

Liu, Jane Jijun ; Druta, Mihaela ; Shibata, David ; Coppola, Domenico ; Boler, Ivette ; Elahi, Abul ; Reich, Richard R. ; Siegel, Erin ; Extermann, Martine. / Metabolic syndrome and colorectal cancer : Is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process?. In: Journal of Geriatric Oncology. 2014 ; Vol. 5, No. 1. pp. 40-48.
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abstract = "Objective: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. Materials and Methods: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6. months after surgery. Results: The MS group had significantly higher baseline and post-operative fasting insulin levels (p. <. 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p. <. 0.001) while IR expression showed no difference. Interestingly, 64{\%} of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumor IGF-1R over-expression (80{\%}) was confirmed, but there was no difference between MS and non-MS patients. Tumor RAGE over-expression was found in 67{\%} of patients and was equally distributed between the two groups. Conclusions: Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.",
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T2 - Is hyperinsulinemia/insulin receptor-mediated angiogenesis a critical process?

AU - Liu, Jane Jijun

AU - Druta, Mihaela

AU - Shibata, David

AU - Coppola, Domenico

AU - Boler, Ivette

AU - Elahi, Abul

AU - Reich, Richard R.

AU - Siegel, Erin

AU - Extermann, Martine

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N2 - Objective: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. Materials and Methods: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6. months after surgery. Results: The MS group had significantly higher baseline and post-operative fasting insulin levels (p. <. 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p. <. 0.001) while IR expression showed no difference. Interestingly, 64% of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumor IGF-1R over-expression (80%) was confirmed, but there was no difference between MS and non-MS patients. Tumor RAGE over-expression was found in 67% of patients and was equally distributed between the two groups. Conclusions: Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.

AB - Objective: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. Materials and Methods: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6. months after surgery. Results: The MS group had significantly higher baseline and post-operative fasting insulin levels (p. <. 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p. <. 0.001) while IR expression showed no difference. Interestingly, 64% of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumor IGF-1R over-expression (80%) was confirmed, but there was no difference between MS and non-MS patients. Tumor RAGE over-expression was found in 67% of patients and was equally distributed between the two groups. Conclusions: Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.

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