Lymphangiogenesis in colorectal cancer—Prognostic and therapeutic aspects

Abstract

Colorectal cancer (CRC) represents the second most common cause of cancer mortality in the western world. The tumors frequently show metastatic spread which affects different organs such as lymph nodes, liver and lungs. Although the pattern of spread may vary, the initial step usually involves dissemination to regional lymph nodes. At present it is clear that neovessel formation, including lymphangiogenesis, represents key events in tumor progression. However, to what extent lymphangiogenesis contributes in the progression of CRC is unclear. This work focuses on recent progress within the field of tumor lymphangiogenesis with special reference to CRC, and on novel therapeutic strategies for anti-lymphangiogenic therapies. Inhibition of metastatic spread may be achieved by restriction of lymphatic vessel growth by using targeted therapeutic strategies towards molecules involved in lymphangiogenic signalling. Such adjuvant therapeutic approaches in addition to existing therapeutic strategies may represent a favourable treatment for CRCs with higher than average risk of disease recurrence and progression. ' 2007 Wiley-Liss, Inc.

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

“…15 In particular, CRC-associated stromal fibroblasts have been found to upregulate vascular endothelial growth factor (VEGF-A), which is significantly correlated with lymphovascular invasion (LVI), angiogenic spread and poor prognosis. [16][17][18] LVI in CRC has been linked to lymph node metastasis 19,20 and liver metastasis; 21 hence, accurate assessment of LVI in primary CRC is important in the diagnosis and treatment of patients. Moreover, because stromal cells of the CRC microenvironment has been found to have an important role in the development of blood and lymphatic vessels associated with LVI, 22 we investigated stromal SPARC expression and its relationship to LVI.…”

Molecular Mechanisms of Lymphatic Metastasis

“…A number of reports describe in CRC a correlation between VEGF-A expression levels and lymph node metastasis (Sundlisaeter, Dicko et al 2007). …”

Pien Tze Huang suppresses VEGF-C-mediated lymphangiogenesis in colorectal cancer

“…Lymphangiogenesis and early regional metastasis frequently occurs in several types of malignant tumors including CRC (5). The density of LVs in or surrounding tumors is closely associated with lymph node metastasis and prognosis of CRC patients (3).…”

“…Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF family, was the first lymphangiogenic growth factor to be identified (5). Mechanistically, the binding of VEGF-C to its cognate receptor VEGFR-3, which is expressed on human lymphatic endothelial cells (HLECs) (6), promotes proliferation and migration of HLECs as well as the formation of LVs (7,8).…”