Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

Vekemans, Katrien; Braet, Filip

doi:10.3748/wjg.11.5095

Cited by 9 publications

(13 citation statements)

References 24 publications

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“…Our previous microscopy and fine structural immunochemistry studies significantly contributed to the above model and as depicted in figure 1 we were able to demonstrate that KC, NK and HECs all work together in concert as one immune-surveillance guardian in the defence against CRC liver metastasis ( Figure 1) [6] . Furthermore, it was shown that phagocytosis and apoptosis are key processes in three central steps in the complex CRC liver metastatic cascade, briefly: (Step Ⅰ) When CC531s colon carcinoma cells encounter the liver sinusoid about 90% of the tumour cells are eliminated by a synergistic action between KC and NK cells [9] ; (Step Ⅱ) We have proven that HECs express FasL and that about 5% of the colorectal CC531s cell population express functional Fas under influence of IFNγ and NO released in the sinusoid by NK and HECs, respectively.…”

Section: Phagocytosis Apoptosis Endothelial Retraction and Tumour Smentioning

confidence: 70%

“…This hepatic sinusoidal immune system involves the hepatic-specific natural killer cells (NK) (pit cells) [3] , Kupffer cells (KC) (liver-associated macrophages) [4] and hepatic endothelial cells (HEC) [5] , and is proven to play an important role in protecting the liver from invading colon carcinoma cells [6] . The conventional paradigm of CRC liver metastasis is based on a multi-step process characterized by a series of structural, cellular and molecular events, which give the tumour cells the ability to proceed through the many phases of liver metastasis.…”

Section: Colorectal Cancer and The Hepatic Sinusoidal Immune Systemmentioning

confidence: 99%

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The hepatic sinusoidal endothelial lining and colorectal liver metastases

Braet¹,

Nagatsuma²,

Saito³

et al. 2007

WJG

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Colorectal cancer (CRC) is a common malignant disease and the severe nature of cases in men and women who develop colorectal cancer makes this an important socio-economic health issue. Major challenges such as understanding and modeling colorectal cancer pathways rely on our understanding of simple models such as outlined in this paper. We discuss that the development of novel standardized approaches of multidimensional (correlative) biomolecular microscopy methods facilitates the collection of (sub) cellular tissue information in the early onset of colorectal liver metastasis and that this approach will be crucial in designing new effective strategies for CRC treatment. The application of X-ray micro-computed tomography and its potential in correlative imaging of the liver vasculature will be discussed.

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Section: Phagocytosis Apoptosis Endothelial Retraction and Tumour Smentioning

confidence: 70%

Section: Colorectal Cancer and The Hepatic Sinusoidal Immune Systemmentioning

confidence: 99%

The hepatic sinusoidal endothelial lining and colorectal liver metastases

Braet¹,

Nagatsuma²,

Saito³

et al. 2007

WJG

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“…Each of these cell types plays a crucial role in hepatic homeostasis and CRC metastasis [113] . The progression of CRC hepatic metastasis is divided into four interrelated phases: (1) microvascular phase of liver-infiltrating malignant cells; (2) interlobular micrometastasis phase; (3) angiogenic micrometastasis phase; and (4) established hepatic metastasis phase.…”

Section: Extravasation -Crc Cell Arrest In the Hepatic Sinusoidsmentioning

confidence: 99%

“…The cells contain granules with lysosomal enzymes, perforin and various phosphatases, but their structural characteristic is the presence of cytoplasmic rod vesicles. Their shape varies, due to the presence of pseudopodia [113,168,169] . Pit cells substantially contribute to hepatic immunity and exert strong antitumour action.…”

Section: Pit Cellsmentioning

confidence: 99%

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Paschos

Majeed

Bird

2014

WJG

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Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting. Paschos KA, Majeed AW, Bird NC. Natural history of hepatic metastases from colorectal cancer -pathobiological pathways with clinical significance.

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“…Leukocyte recruitment upon liver injury [4], [5], [6] as well as liver colonization by metastatic tumor cells [7], [8] are actively influenced by LSECs. The unique morphology as well as the microenvironment-dependent molecular differentiation of LSECs [19] define the organ-specific features of this transendothelial barrier.…”

Section: Introductionmentioning

confidence: 99%

Unique Cell Type-Specific Junctional Complexes in Vascular Endothelium of Human and Rat Liver Sinusoids

et al. 2012

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Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs) using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ), i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ) transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

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Structural and functional aspects of the liver and liver sinusoidal cells in relation to colon carcinoma metastasis

Cited by 9 publications

References 24 publications

The hepatic sinusoidal endothelial lining and colorectal liver metastases

The hepatic sinusoidal endothelial lining and colorectal liver metastases

Natural history of hepatic metastases from colorectal cancer - pathobiological pathways with clinical significance

Unique Cell Type-Specific Junctional Complexes in Vascular Endothelium of Human and Rat Liver Sinusoids

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