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2017 ; 18
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The Pleiotropic Role of L1CAM in Tumor Vasculature
#MMPMID28134764
Angiolini F
; Cavallaro U
Int J Mol Sci
2017[Jan]; 18
(2
): ä PMID28134764
show ga
Angiogenesis, the formation of new vessels, is a key step in the development,
invasion, and dissemination of solid tumors and, therefore, represents a viable
target in the context of antitumor therapy. Indeed, antiangiogenic approaches
have given promising results in preclinical models and entered the clinical
practice. However, in patients, the results obtained so far with antiangiogenic
drugs have not completely fulfilled expectations, especially because their effect
has been transient with tumors developing resistance and evasion mechanisms. A
better understanding of the mechanisms that underlie tumor vascularization and
the functional regulation of cancer vessels is a prerequisite for the development
of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule
(L1CAM), a cell surface glycoprotein previously implicated in the development and
plasticity of the nervous system, is aberrantly expressed in the vasculature of
various cancer types. L1CAM plays multiple pro-angiogenic roles in the
endothelial cells of tumor-associated vessels, thus emerging as a potential
therapeutic target. In addition, L1CAM prevents the maturation of cancer
vasculature and its inhibition promotes vessel normalization, a process that is
thought to improve the therapeutic response of tumors to cytotoxic drugs. We here
provide an overview on tumor angiogenesis and antiangiogenic therapies and
summarize the current knowledge on the biological role of L1CAM in cancer
vasculature. Finally, we highlight the clinical implications of targeting L1CAM
as a novel antiangiogenic and vessel-normalizing approach.
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