Possible paracrine mechanism of insulin-like growth factor-2 in the development of liver metastases from colorectal carcinoma.

Abstract

BACKGROUND:

Insulin-like growth factor-2 (IGF-2) is considered one of the autocrine growth factors in colorectal carcinoma. In addition, it is well known that IGF-2 is produced in the liver. However, the role of IGF-2 in liver metastasis is not yet understood clearly.

METHODS:

Immunohistochemical staining of IGF-2 and IGF-1 receptor (IGF-1R) was performed on tissue samples of liver metastases from 30 colorectal carcinoma patients. In situ hybridization of IGF-2 also was conducted on the same tissue samples. Furthermore, proliferating cell nuclear antigen (PCNA) was immunohistochemically stained for use as an indicator of the proliferative activity of cancer cells.

RESULTS:

Invasive margins of liver metastases were stained highly by both IGF-2 (70%) and IGF-1R (83%). Overexpression of IGF-2 protein and mRNA was observed in the normal liver adjacent to the tumor. The PCNA labeling indices (LIs) of the IGF-2 positive groups were significantly higher than those of the IGF-2 negative group (P < 0.0001). In addition, the PCNA LIs for the IGF-1R positive groups also were significantly higher than those for the IGF-1R negative group (P=0.0002).

CONCLUSIONS:

These findings suggest that hepatocyte-derived IGF-2 stimulates tumor cell proliferation by a paracrine mechanism and plays an important role in tumor progression in colorectal carcinoma patients with liver metastases.

• Authors: K Kawamoto, H Onodera, S Kan, S Kondo, M Imamura
• Journal: Cancer (Cancer) Vol. 85 Issue 1 Pg. 18-25 (Jan 01 1999) ISSN: 0008-543X [Print] United States
• PMID: 9921969 (Publication Type: Journal Article)

Chemical References

• Proliferating Cell Nuclear Antigen
• Insulin-Like Growth Factor II
• Receptor, IGF Type 1

Topics

• Aged
• Colorectal Neoplasms (chemistry, pathology)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• In Situ Hybridization
• Insulin-Like Growth Factor II (analysis, physiology)
• Liver (chemistry)
• Liver Neoplasms (chemistry, secondary)
• Male
• Middle Aged
• Proliferating Cell Nuclear Antigen (analysis)
• Receptor, IGF Type 1 (analysis)