Lymphangiogenesis and Its Relationship With Lymphatic Metastasis and Prognosis in Malignant Melanoma

Abstract

Regional lymph node metastasis is one of the important indicators of cutaneous malignant melanoma.

Lentivirus‐Mediated Small Interfering RNA Targeting VEGF‐C Inhibited Tumor Lymphangiogenesis and Growth in Breast Carcinoma

“…Experiments with transgenic mice have shown that overexpression of VEGF-C results in lymphatic endothelial proliferation and vessel enlargement (Jeltsch et al, 1997). Likewise, the clinical significance of VEGF-C expression in relation to lymph node metastasis and patient outcome has been reported in cancers of the esophagus, stomach, and colorectum (Liu et al, 2008). Downregulation of VEGF-C or blockade of VEGFR-3 signaling inhibits lymphangiogenesis and lymph node metastasis in experimental animal cancer models (Chen et al, 2005;Lin et al, 2005;Burton et al, 2008).…”

“…Although tumor cell dissemination is mediated by a number of mechanisms, the most common pathway of initial dissemination is through the lymphatic system to the regional lymph nodes (Pepper et al, 2000). The presence of metastases in regional lymph nodes is a strong indicator of low-patient survival rate, poor patient prognosis in many types of cancer (Skobe et al, 2001;Miyahara et al, 2007;Liu et al, 2008). Despite advances in the treatment of breast cancer, morbidity and mortality from breast cancer remain unacceptably high.…”

“…Among them, VEGF-C appears to be the most important factor that contributes to lymphangiogenesis and acts via the cognate receptor tyrosine kinase VEGF receptor-3 (VEGFR-3) located on lymphatic endothelial cells (Achen and Stacker, 2008). Increased VEGF-C expression can promote the formation of tumor lymphangiogenesis and increase the metastatic spread of tumor cells to lymph nodes in numerous cancers including breast cancer (Mattila et al, 2002;Tamura and Ohta, 2003;Liu et al, 2008). Transgenic and knock-out mice tumor models indicate that VEGF-C is a vital factor in tumor lymphangiogenesis and the subsequent formation of lymph node metastasis (Mandriota et al, 2001;Karkkainen et al, 2004).…”

Lymphangiogenesis and Anti-lymphangiogenesis in Cutaneous Melanoma

“…VEGF-C was immunohistochemically detected in the cytoplasm of malignant cells in 70.97% of metastatic melanoma cases and 36% of non-metastatic cases (20). Current evidence demonstrate the correlation between VEGF-C overexpression in the primary tumor and existence of lymph node metastases (36).…”

“…Also, in most studies, higher LMVD values were observed in the peritumor zone than the intratumor zone, along with significant morphologialc differences. The number of peritumor lymphatic vessels is significantly larger in cases of VEGF-C and -D positive malignant melanomas than in the negative ones (10.05 vs. 6.4 and 10.07 vs. 6.3, respectively) (20). As a particularity, LMVD values may represent a discriminating aspect between metastatic malignant melanoma versus the non-metastatic one (12.8 and 5.9, respectively) (21).…”