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The Tumor Microenvironment at Different Stages of Hepatic Metastasis

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Liver Metastasis: Biology and Clinical Management

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

Abstract

This chapter summarizes current knowledge on the contribution of architectural and functional aspects of the hepatic tissue to cancer cell regulation during the process of hepatic metastasis. To this end, four consecutive phases in the process, each with distinct mechanisms, have been considered: (1) The microvascular phase of liver-infiltrating cancer cells that includes mechanisms of intravascular arrest, death or survival of cancer cells at specific sites of the hepatic microcirculation and their interactions with organ-specific microvascular endothelial and blood cells; (2) The pre-angiogenic, intralobular micrometastatic phase that includes activation of cancer cell growth, regional anti-tumor immune response impairment and stromal cell recruitment into avascular micrometastases; (3) The angiogenic panlobular micrometastatic phase that includes hypoxic stromal myofibroblasts–induced recruitment of endothelial cells, blood vessel formation and hepatic tissue replacement or “pushing-type” cancer cell growth; and (4) The lobar growth phase of hepatic metastases. During this final phase, the clinical impact and prognostic significance of the metastatic process are determined by multiple factors including the intratumoral stroma and angiogenic patterns, the phenotypes of tumor-infiltrating lymphocytes and the specific gene expression profiles of the metastatic cancer cells. In addition, alterations in the local microenvironment during liver inflammation, regeneration and fibrosis provide a favorable milieu for cancer metastasis and their impact is therefore also discussed. Resident hepatic cells and invading cancer cells can reciprocally alter each other’s gene expression profiles and functional activities during the metastatic process. The characterization of these molecular changes could lead to identification of novel biomarkers and therapeutic targets that are involved at discrete stages of hepatic metastasis and thereby impact the clinical management of liver metastases.

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Abbreviations

SMA:

α-smooth muscle actin

CEA:

carcinoembryonic antigen

COX:

cyclooxygenase

DDR2:

discoidin domain receptor-2

HSEC:

hepatic sinusoidal endothelial cells

HSC:

hepatic stellate cells

ICE:

IL-1 converting enzyme

ManR:

mannose receptor

NK:

natural killer

TLR:

toll-like receptor

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Acknowledgements

The author acknowledges with gratitude Dr. Pnina Brodt’s significant editorial contribution to this chapter.

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  1. Institute of Applied Molecular Medicine (IMMA), CEU-San Pablo University School of Medicine, Urb. Montepríncipe, Boadilla del Monte, 28668, Madrid, Spain

    Fernando Vidal-Vanaclocha

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  1. Fernando Vidal-Vanaclocha
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Correspondence to Fernando Vidal-Vanaclocha .

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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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Vidal-Vanaclocha, F. (2011). The Tumor Microenvironment at Different Stages of Hepatic Metastasis. 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_3

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