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Review
. 2015 Jan 22;3(1):71-88.
doi: 10.3390/biomedicines3010071.

HGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation

Anna Spina  1 , Valeria De Pasquale  2 , Giuliana Cerulo  3   4 , Pasquale Cocchiaro  5   6 , Rossella Della Morte  7 , Luigi Avallone  8 , Luigi Michele Pavone  9
Affiliations
Review

HGF/c-MET Axis in Tumor Microenvironment and Metastasis Formation

Anna Spina et al. Biomedicines. .

Abstract

Tumor metastases are responsible for approximately 90% of all cancer-related deaths. Metastasis formation is a multistep process that requires acquisition by tumor cells of a malignant phenotype that allows them to escape from the primary tumor site and invade other organs. Each step of this mechanism involves a deep crosstalk between tumor cells and their microenvironment where the host cells play a key role in influencing metastatic behavior through the release of many secreted factors. Among these signaling molecules, Hepatocyte Growth Factor (HGF) is released by many cell types of the tumor microenvironment to target its receptor c-MET within the cells of the primary tumor. Many studies reveal that HGF/c-MET axis is implicated in various human cancers, and genetic and epigenetic gain of functions of this signaling contributes to cancer development through a variety of mechanisms. In this review, we describe the specific types of cells in the tumor microenvironment that release HGF in order to promote the metastatic outgrowth through the activation of extracellular matrix remodeling, inflammation, migration, angiogenesis, and invasion. We dissect the potential use of new molecules that interfere with the HGF/c-MET axis as therapeutic targets for future clinical trials in cancer disease.

Keywords: HGF; c-MET; cancer; metastasis; microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Formation of the tumor microenvironment.
Figure 2
Figure 2
Inflammatory signaling in the tumor microenvironment.
Figure 3
Figure 3
Invasive and metastatic signaling from the tumor microenvironment.
Figure 4
Figure 4
HGF/c-MET major signaling in tumor invasion.
See this image and copyright information in PMC

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