Pathways Targeting Tumor Lymphangiogenesis

Abstract

Tumor metastasis to sentinel lymph nodes represents the first step of tumor dissemination in most human cancers and serves as a major prognostic indicator for disease progression. Recent studies have revealed that tumors can actively induce the formation of lymphatic vessels, and that tumor lymphangiogenesis is correlated with lymph node metastasis in experimental cancer models and in several types of human cancers.

Angiogenesis and lymphangiogenesis are downregulated in primary breast cancer

“…Besides their ability to induce angiogenesis, tumours can also induce the formation of new lymphatic vessels, a process referred to as lymphangiogenesis (Wissmann and Detmar, 2006;Karpanen and Alitalo, 2008). Lymphangiogenesis is mainly stimulated by VEGF-C and VEGF-D, and also VEGF-A, HGF as well as members of the FGF, angiopoietin, PDGF and insulin-like growth factor families can support this process.…”

Disruption of VEGF Mediated Flk‐1 Signaling Leads to a Gradual Loss of Vessel Health and Cardiac Function During Myocardial Infarction: Potential Therapy With Pellino‐1

“…There was also a significant difference in phosphorylation of Flk‐1 expression (p‐Flk‐1/Flk‐1) in the Flk‐1 +/− MI group (1.6‐fold) compared with WTMI (Figure 1A and 1F). We also investigated the effect of downregulation of Flk‐1 on Akt and eNOS expression (both nonphosphorylated and phosphorylated forms) because PI3K/Akt/eNOS signaling is known to play an important role downstream of Flk‐1 (VEGFR2) 24, 25, 26, 27. Akt phosphorylation at the Ser 473 site was significantly reduced in both the WTMI (1.6‐fold) and Flk‐1 +/− MI (6.1‐fold) groups compared with WTS.…”

New Model of In-situ Xenograft Lymphangiogenesis by a Human Colonic Adenocarcinoma Cell Line in Nude Mice

“…LYVE-1 (Jackson et al, 2001;Prevo et al, 2001;, D2-40 (Breiteneder et al, 1999;Renyi et al, 2000;Kowanetz and Ferrara, 2006;Wissmann and Detmar, 2006) are the most important lymphatic endothelial cell-specific markers. While LYVE-1, D2-40 and VEGFR-3 expression is positive lymphangiogenesis rather than angiogenesis.…”

“…While LYVE-1, D2-40 and VEGFR-3 expression is positive lymphangiogenesis rather than angiogenesis. VEGF-C and VEGF-D and VEGFR-3 are recognized as lymphatic endothelial growth factor and receptors in the lymphatic-VEGFR-3 signaling pathway (Kubo et al, 2000;Kowanetz and Ferrara, 2006;Wissmann and Detmar, 2006;Sundar and Ganesan, 2007;Nagahashi et al, 2010). Our results suggest that the models of orthotopic transplantation of colorectal cancer in nude mice showed LYVE-1, D2-40 immunohistochemical staining strongly positive, LYVE-1, D2-40, VEGF-C, VEGF-D and VEGFR-3 protein capillaries and the VEGF-C, -D/VEGFR-3 signaling axis control mechanism, which proved that the model of orthotopic transplantation of colorectal cancer in nude mice was a colorectal adenocarcinoma lymphangiogenesis animal model.…”

“…Recent studies have found that lymphangiogenesis is a major factor and mechanism for colorectal cancer lymphatic metastasis and recurrence Sundar and Ganesan, 2007;Nagahashi et al, 2010). With the lymphatic vessels, technological progress to define mechanism of lymphangiogenesis, it has been taken attach of the relationship between molecular mechanism of lymphangiogenesis and lymphatic metastasis, as well as the therapy based on antilymphangiogenesis (McColl et al, 2005;Wissmann and Detmar, 2006). In order to study lymphatic metastasis in colorectal cancer and antilymphangiogenic treatment, it is imperative to establish a line of lymphangiogenic animal models to research human colorectal cancer (Fidler, 2003).…”