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Vasculogenic mimicry: Possible role of effector caspase-3, caspase-6 and caspase-7

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Abstract

Vasculogenic mimicry (VM) describes the process by which aggressive cancer cells form extracellular matrix-rich, vessel-like mesh works, which supply nutrients and oxygen. Furthermore, it offers a new route for tumor cell invasion and metastasis and thus a correspondingly poor prognosis and survival rate for affected patients. Effector caspases are well known for their apoptotic function, whereas a non-apoptotic function in tumor progression is highly disputed. Caspase-3, -6 and -7 are expressed in aggressive tumor cells in a non-mutated form, indicating an active function independent of apoptosis. This review summarizes the possible functions of the above-mentioned caspases in VM. We also discuss the possible involvement of caspases in potential mechanisms towards the formation of vessel-like structures. Furthermore, this review illustrates the importance of new studies in the ongoing investigation into the role of effector caspases in VM, invasion, and migration of aggressive tumor cells.

Section snippets

Vasculogenic mimicry—Discovery and characteristics

It is well known that the supply of oxygen and nutrients via connection to the blood circulation system is an essential factor in tumor growth and metastasis (Hanahan and Weinberg, 2011, Hanahan and Weinberg, 2000). In addition to tumor angiogenesis, aggressive tumor cells may possess another independent mechanism for generating blood supply called vasculogenic mimicry (VM) (Folberg and Maniotis, 2004, Maniotis et al., 1999). VM describes the ability of aggressive cancer cells to form

Function and mechanism of effector caspases in VM

The class of effector caspases consists of caspase-3, -6 and -7, which are all known to play a crucial role in apoptosis (Jiaqi and Juan, 2002, Porter and Jänicke, 1999). In contrast, several researchers have revealed non-apoptotic functions, including proliferation, migration, and differentiation in normal tissues as well as in tumor cells (Shalini et al., 2014). A study by Ishizaki et al. (1998), for example, demonstrated a connection between caspase-3 activity and the enucleation of

Conclusion

In this paper we have summarized the possible role of effector caspase-3, caspase-6 and caspase-7 in the formation of vessel-like, ECM-rich structures of aggressive tumor cells. We have additionally reviewed different mechanisms by which these caspases may contribute to VM. The summary of our investigation is that caspase-3, caspase-6 and caspase-7 may exercise an important function in tumorigenesis, particular in vasculogenic mimicry. However, at present, only the connection of caspase-3 to VM

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