Lymphangiogenesis and Anti-lymphangiogenesis in Cutaneous Melanoma

Abstract

Abstract. Cutaneous malignant melanoma is an aggressive tumor characterized by early lymph node metastasis and bad prognosis. Although the spread of tumor cells in the regionalDespite the latest efforts concerning early detection, both the incidence and mortality caused by malignant melanoma of the skin, continue to grow. Malignant melanoma represents less that 10% of all cutaneous tumors, which is, however, responsible for most deaths caused by tumors of the skin. The natural evolution of malignant melanoma depends on its metastatic dissemination that is, in turn, influenced by multiple factors, particularly the thickness of the tumor, its localization and pathological subtype. Malignant melanomas of the skin are characterized, amongst other things, by early lymphatic dissemination in the regional lymph nodes and by lymph node metastases that significantly influence their staging, prognosis and clinical approach. As a matter of fact, the detection of micrometastases in the sentinel lymph node is of prognostic value and represents the most important predictive criterion for survival in patients with no clinical evidence of lymph node metastases. Moreover, the global survival of patients lacking lymph node metastases is over 85% in a 10-year follow-up and that of patients with positive lymph nodes is less than 45% (1). Once lymph node metastases become clinically obvious, 75-80% of patients already have other distant metastases. It is notable that 15% of the patients diagnosed with thin malignant melanoma (less than 1 mm) develop metastases. At the time being, there are no highly specific predictive indicators for metastases development in patients diagnosed with melanoma.

Exosomes as a Communication Tool Between the Lymphatic System and Bladder Cancer

“…Although the molecular and cellular mechanisms that control these processes have not yet been completely identified, the remodeling of tumor-associated lymphatics has been reported to provide important clinical information on metastasis and prognosis. In the case of metastatic melanomas with enlarged tumor-associated lymphatics, the lymphatic vessel area was significantly associated with poor disease-free and overall survival [ 6 , 7 ]. Thus, targeting lymphangiogenesis through inhibiting lymphangiogenic signaling pathways could be a potential tool for blocking or delaying metastasis.…”

Metastatic Gallbladder Melanoma Presenting as Acute Emphysematous Cholecystitis

“…There are no large case series or reviews of collected experience to be able to compare the number of asymptomatic to symptomatic cases. Dissemination of malignant cells to distant sites occurs most commonly via regional lymph nodes [ 7 ]. Hematogenous spread is less frequent.…”

Cellular and Molecular Heterogeneity Associated with Vessel Formation Processes

“…In view of this knowledge, as well as in angiogenesis, some therapeutic strategies involving the use of antilymphangiogenic agents and blocking of VEGF signalling have been proposed and studied to successfully inhibit tumour growth. Anti-VEGF and anti-VEGF-C monoclonal antibodies, as well as antibodies against specific parts of the VEGFR-2 receptor, were produced, yet there are no approved drugs able to only block lymphangiogenesis, which could benefit some pathologies that do not necessarily require the blocking of angiogenic processes [ 183 , 184 ].…”