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Role of CXC Chemokines and Receptors in Liver Metastasis – Impact on Liver Resection-Induced Engraftment and Tumor Growth

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Liver Metastasis: Biology and Clinical Management

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 16))

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Abstract

Chemokines are inflammatory cytokines that stimulate the migration of distinct subsets of cells including tumor cells. The chemokines MIP (macrophage inflammatory protein)-2 and SDF (stromal cell-derived factor)-1 that are both members of the CXC chemokine superfamily have an important impact on tumor progression and metastasis of colorectal cancer. Our experimental studies demonstrate that chemotactic signaling does not only contribute to the metastatic spread of tumor cells, but is also essential for tumor engraftment and progression. These studies on chemokines have exceeded the previous expectations in elucidating homing mechanisms directing colorectal cancer metastasis and have given us a deeper insight into the mechanisms that regulate tumor growth. Chemotactic signaling is necessary for a variety of physiological and pathological processes including inflammatory response, leukocyte traffic, angiogenesis and programmed cell death. Therefore, it seems very unlikely that targeting one single chemokine will be sufficient as a single modality therapy for cancer treatment. The complex network of chemokines and chemokine receptors could provide compensatory mechanisms to overcome permanent deprivation of a specific chemokine, as we already demonstrated for MIP-2 and SDF-1. Our findings thus far encourage further investigation. The chemotactic signaling in cancer is a new and promising target/perspective for anti-tumor therapy.

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Abbreviations

ENA-78:

epithelial neutrophil-activating protein-78

GCP-2:

granulocyte chemotactic protein-2

GFP:

green fluorescent protein

GRO-α/-β/-γ:

growth-related oncogene-α/-β/-γ

HCC:

hepatocellular carcinoma

IL-8:

interleukin-8

I-TAC:

interferon-inducible T-cell alpha chemoattractant

MCP-1:

monocyte chemotactic protein-1

MIP-2:

macrophage inflammatory protein-2

PF-4:

platelet factor-4

SDF-1:

stromal cell-derived factor-1

TGF-α/-β:

transforming growth factor-α/-β

TNF-α:

tumour necrosis factor-α

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, D-66421, Homburg/Saar, Germany

    Otto Kollmar

  2. Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany

    Otto Kollmar & Michael D. Menger

  3. Department of General, Visceral, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany

    Martin K. Schilling

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  1. Otto Kollmar
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  2. Michael D. Menger
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  3. Martin K. Schilling
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Correspondence to Otto Kollmar .

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  1. Royal Victoria Hospital, Division of Surgical Research, McGill University Health Centre, Pine Ave W. 687, Montreal, H3A 1A1, Québec, Canada

    Pnina Brodt

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Kollmar, O., Menger, M.D., Schilling, M.K. (2011). Role of CXC Chemokines and Receptors in Liver Metastasis – Impact on Liver Resection-Induced Engraftment and Tumor Growth. In: Brodt, P. (eds) Liver Metastasis: Biology and Clinical Management. Cancer Metastasis - Biology and Treatment, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0292-9_5

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