Malignant cell interactions with cells of the hepatic sinusoids mediate primarily the development of colorectal cancer liver metastasis

Abstract

Metastases are the main cause of death for patients with
colorectal cancer and the liver is the primary host organ.
However, macrometastases constitute the final step of a complicated
and poorly-defined multistage process, named invasion-
metastasis cascade. Before they metastasise, malignant
cells undergo partial or complete transformation and acquire
new properties. They present intensive growth, provoke neoangiogenesis,
invade the surrounding extracellular matrix,
detach from their primary site and intravasate. Some succeed
in surviving in the systemic circulation, adhere to hepatic sinusoids
and extravasate. Eventually, by evading the hepatic
immune system, few cancer cells colonise the liver and form
metastases. While a vast number of cells leave the primary
tumour and intravasate, only a small minority reaches the
liver blood network. Thus, the possibility of metastases formation
is very low. The entrapment of colorectal cancer cells
in the sinusoids and their interactions with the resident cells
are considered very important initial steps in the liver invasion.
Sinusoidal endothelial cells, pit cells, stellate cells and
Kupffer cells all mediate the metastatic process in complex
ways, through a variety of biological compounds and intercellular actions. Current research aims to elucidate the role of these cells in colorectal cancer liver metastasis.