Lymphangiogenesis: a new player in cancer progression

Abstract

Lymph node metastasis is the hallmark of colon cancer progression, and is considered one of the most important prognostic factors. Recently, there has been growing evidence that tumor lymphangiogenesis (formation of new lymphatic vessels) plays an important role in this process. Here, we review the latest findings of the role of lymphangiogenesis in colorectal cancer progression, and discuss its clinical application as a biomarker and target for new therapy. Understanding the molecular pathways that regulate lymphangiogenesis is mandatory to pave the way for the development of new therapies for cancer. In the future, tailored treatments consisting of combinations of chemotherapy, other targeted therapies, and anti-lymphangiogenesis agents will hopefully improve patient outcomes. This progression to the clinic must be guided by new avenues of research, such as the identification of biomarkers that predict response to treatment.

Figure 1

Lymphangiogenic growth factors and their receptors expressed by lymphatic endothelium. Vascular endothelial growth factor (VEGF) receptor (VEGFR)-3 is a member of the fms-like tyrosine kinase family and specifically binds VEGF-C and VEGF-D, but not VEGF-A. Recent studies also indicate an important role for the VEGF-A/VEGFR-2 signaling pathway in lymphangiogenesis.

Figure 2

Limitations of lymphatic vessel density estimations. The central section of a tumor with a necrotic central core may estimate a misleadingly low lymphatic vessel density (LVD) (left), while the peripheral section of the same tumor may estimate a misleadingly high LVD (right).