Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11825
Title: Tumour growth stimulation following partial hepatectomy in mice is associated with increased upregulation of c-Met.
Authors: Harun, Nadia;Costa, Patricia;Christophi, Christopher
Affiliation: Department of Surgery, AH/NH Austin Hospital, University of Melbourne, Heidelberg, VIC, 3084, Australia
Issue Date: 31-Jul-2013
Citation: Clinical & Experimental Metastasis 2013; 31(1): 1-14
Abstract: Hepatic resection is the preferred option for curative treatment of colorectal liver metastasis (CLM). However, this is associated with significant recurrence rates in both hepatic and extrahepatic sites. The upregulation of growth factors required for liver regeneration after resection is thought to stimulate the growth of micrometastases. The current study describes temporal changes in the expression of hepatocyte growth factor receptor (c-Met), epidermal growth factor receptor (EGFR) and insulin growth factor I receptor (IGF-IR) in an orthotopic mouse model of liver resection and tumour induction. Mice underwent 70% hepatectomy and induction of liver metastases through intrasplenic injection of colorectal cancer cells. Control groups included sham-operated mice and 70% hepatectomy alone. The expression levels of liver and tumour c-Met, EGFR and IGF-IR were quantified by quantitative RT-PCR at different time points. 70% liver resection stimulates tumour growth; increases the expression of c-Met within established tumours and surrounding liver parenchyma; downregulates EGFR expression and increases IGF-IR expression within the liver parenchyma. In conclusion, we demonstrate in our mouse model that major hepatectomy stimulates engraftment and growth of CLM and that this effect is probably due to the upregulation of c-Met as a result of the liver regeneration process. Liver IGF-IR may also contribute to this phenomenon through a paracrine effect on tumour growth. This study provides support for the role of c-Met in the stimulation of tumour growth after resection possibly through the promotion of tumour cell proliferation.
Internal ID Number: 23900501
URI: http://ahro.austin.org.au/austinjspui/handle/1/11825
DOI: 10.1007/s10585-013-9604-7
URL: http://www.ncbi.nlm.nih.gov/pubmed/23900501
Type: Journal Article
Subjects: Animals
Cell Proliferation
Colorectal Neoplasms.metabolism.pathology
Disease Models, Animal
Hepatectomy
Immunohistochemistry
Insulin-Like Growth Factor I.biosynthesis
Liver Neoplasms.metabolism.secondary.surgery
Liver Regeneration.physiology
Male
Mice
Mice, Inbred CBA
Proto-Oncogene Proteins c-met.biosynthesis
RNA, Messenger.analysis
Receptor, Epidermal Growth Factor.biosynthesis
Reverse Transcriptase Polymerase Chain Reaction
Up-Regulation
Appears in Collections:Journal articles

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