Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/11801
Title: Bimodal role of Kupffer cells during colorectal cancer liver metastasis.
Authors: Wen, Shu Wen;Ager, Eleanor I;Christophi, Christopher
Affiliation: Department of Surgery, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
ShuWen.Wen@qimr.edu.au
Issue Date: 10-May-2013
Citation: Cancer Biology & Therapy 2013; 14(7): 606-13
Abstract: Kupffer cells (KCs) are resident liver macrophages that play a crucial role in liver homeostasis and in the pathogenesis of liver disease. Evidence suggests KCs have both stimulatory and inhibitory functions during tumor development but the extent of these functions remains to be defined. Using KC depletion studies in an orthotopic murine model of colorectal cancer (CRC) liver metastases we demonstrated the bimodal role of KCs in determining tumor growth. KC depletion with gadolinium chloride before tumor induction was associated with an increased tumor burden during the exponential growth phase. In contrast, KC depletion at the late stage of tumor growth (day 18) decreased liver tumor load compared with non-depleted animals. This suggests KCs exhibit an early inhibitory and a later stimulatory effect. These two opposing functions were associated with changes in iNOS and VEGF expression as well as T-cell infiltration. KC depletion at day 18 increased numbers of CD3 (+) T cells and iNOS-expressing infiltrating cells in the tumor, but decreased the number of VEGF-expressing infiltrating cells. These alterations may be responsible for the observed reduction in tumor burden following depletion of pro-tumor KCs at the late stage of metastatic growth. Taken together, our results indicate that the bimodal role of KC activity in liver tumors may provide the key to timing immunomodulatory intervention for the treatment of CRC liver metastases.
Internal ID Number: 23792646
URI: http://ahro.austin.org.au/austinjspui/handle/1/11801
DOI: 10.4161/cbt.24593
URL: http://www.ncbi.nlm.nih.gov/pubmed/23792646
Type: Journal Article
Subjects: Kupffer cell
colorectal cancer
liver metastases
macrophage
tumor-associated macrophages
Animals
Colorectal Neoplasms.metabolism.pathology
Humans
Kupffer Cells.metabolism.pathology
Liver Neoplasms, Experimental.metabolism.pathology.secondary
Mice
Neoplasm Metastasis
Appears in Collections:Journal articles

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