Angiogenesis, lymphangiogenesis, and melanoma metastasis

Streit, Michael; Detmar, Michael

doi:10.1038/sj.onc.1206457

Cited by 204 publications

(162 citation statements)

References 86 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…These studies were confirmed in later studies (Hubler & Wolf, 1976). Rapid angiogenesis of cutaneous melanomas dramatically enhances the risk of lethality and contributes to the progression of the most common type of young adults (Streit & Detmar, 2003). …”

Section: Angiogenesis and Human Melanomasupporting

confidence: 66%

Role of Angiogenesis and Microenvironment in Melanoma Progression

Ria¹,

Reale²,

Vacca³

2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

View full text Add to dashboard Cite

Section: Angiogenesis and Human Melanomasupporting

confidence: 66%

Role of Angiogenesis and Microenvironment in Melanoma Progression

Ria¹,

Reale²,

Vacca³

2011

Research on Melanoma - A Glimpse Into Current Directions and Future Trends

View full text Add to dashboard Cite

“…However, previous literature have reported controversial findings on the role of angiogenesis as a prognostic factor in melanoma. 34 Contrasting results might be due to the variability of nonstandardized assessment of tumor vascularity and different detection methods used to visualize tumor-associated blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Inducible nitric oxide synthase expression in melanoma: implications in lymphangiogenesis

et al. 2009

View full text Add to dashboard Cite

Cutaneous melanoma preferentially metastasizes via the lymphatic route. However, the mechanisms of lymphatic invasion and metastasis to regional lymph nodes are poorly understood. Nitric oxide is a free radical molecule synthesized from L-arginine by nitric oxide synthases that plays a critical role in various physiological and pathological processes, including tumor growth and angiogenesis. We have tested whether inducible nitric oxide synthase expression correlates with lymphatic vessel density identified with D2-40 antibody and/or blood microvessel density identified with CD105/endoglin in a series of melanocytic nevi (n ¼ 28) and cutaneous melanomas (n ¼ 38), representative of various pT. Inducible nitric oxide synthase expression was significantly lower in melanocytic nevi in comparison with primary and metastatic melanomas (Po0.001). Mean microvessel density was significantly higher in primary and metastatic melanomas in comparison with melanocytic nevi (Po0.001 for intratumoral and P ¼ 0.001 for peritumoral vessels). Vertical growth phase melanomas showed a higher intratumoral microvessel density in comparison with radial growth phase melanomas (P ¼ 0.02). The number of peritumoral lymphatics was significantly lower in nevi as compared with primary and metastatic melanomas (P ¼ 0.01). No correlation between microvessel or lymphatic vessel and clinical outcome was found in melanomas. A significant direct correlation was observed between inducible nitric oxide synthase immunostaining in melanocytic tumor cells and the density of lymphatic vessels (peritumoral: P ¼ 0.001; intratumoral: P ¼ 0.08), and the density of peritumoral blood microvessel (P ¼ 0.02). Our findings support the hypothesis that inducible nitric oxide synthase is implicated not only in blood, but also in lymphatic vascular neoformation in melanoma. Mechanistic studies are needed to address the possibility that inducible nitric oxide synthase controls lymphangiogenesis, dissemination and lymphatic borne metastases. Keywords: iNOS; CD105; D2-40; microvessel density; melanoma; nevi Cutaneous melanoma metastasizes at least initially through the lymphatic route and lymph node metastasis is currently still a major determinant for patients staging and clinical management. The mechanisms of lymphatic invasion and metastasis to regional lymph nodes are mostly unknown and whether human tumors promote de novo lymphangiogenesis is still unclear. Although the pathways that regulate tumorrelated angiogenesis have been partially investigated, poor information is available on the processes that result in lymphangiogenesis in melanoma.Nitric oxide (NO) is a diatomic free radical molecule synthesized from L-arginine by NO synthases (NOS) that plays a critical role in various physiological and pathological processes, including tumor growth. Although the Ca 2 þ -dependent isoforms NOS1 and NOS3 are constitutively expressed by neural and endothelial cells, the Ca 2 þ -independent form (NOS2 or iNOS) can be induced by many cell types upon stimulation by inflamma...

show abstract

“…13 Although the regulators of angiogenesis biologically relevant for melanoma remain unclear, several hypoxia-inducible angiogenic factors, such as basic fibroblast growth factor, vascular endothelial growth factor, interleukin-8, and angiogenin, show enhanced expression in melanoma metastases in vivo and in highly metastatic cell lines. 12,14,31,32 Therefore, antiangiogenic strategy targeting tumor vasculature may hold promise for the treatment of primary and metastatic melanomas. Clinical trials of antiangiogenic therapy for patients with advanced malignant melanoma are currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model

Lee

Shiau

2004

Cancer Gene Ther

View full text Add to dashboard Cite

Some anaerobic and facultative anaerobic bacteria have been used experimentally as anticancer agents because of their selective growth in the hypoxia regions of solid tumors after systemic administration. We have previously shown the feasibility of using attenuated Salmonella choleraesuis as a gene delivery vector. In this study, we exploited S. choleraesuis carrying thrombospondin-1 (TSP-1) gene for treating primary melanoma and experimental pulmonary metastasis in the syngeneic murine B16F10 melanoma model. Systemic administration of S. choleraesuis allowed targeted gene delivery to tumors. The bacteria accumulated preferentially in tumors over livers and spleens at ratios ranging from 1000:1 to 10,000:1. The level of transgene expression via S. choleraesuis-mediated gene transfer in tumors could reach more than 1800-fold higher than in livers and spleens. Notably, bacterial accumulation was also observed in the lungs with metastatic nodules, but not in healthy lungs. When administered into mice bearing subcutaneous or pulmonary metastatic melanomas, S. choleraesuis carrying TSP-1 gene significantly inhibited tumor growth and enhanced survival of the mice. Immunohistochemical studies in the tumors from these mice displayed decreased intratumoral microvessel density. Taken together, these findings suggest that TSP-1 gene therapy delivered by S. choleraesuis may be effective for the treatment of primary as well as metastatic melanomas.

show abstract

Angiogenesis, lymphangiogenesis, and melanoma metastasis

Cited by 204 publications

References 86 publications

Role of Angiogenesis and Microenvironment in Melanoma Progression

Role of Angiogenesis and Microenvironment in Melanoma Progression

Inducible nitric oxide synthase expression in melanoma: implications in lymphangiogenesis

Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model

Contact Info

Product

Resources

About