Abstract
Tumor angiogenesis is a process which is traditionally regarded as the tumor’s response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a pre-requisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia-independent mechanisms of tumor angiogenesis in melanoma.
Highlights
Specialty section: This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology
In a xenotransplant model performed in zebrafishes which express eGFP under the flk1 promoter, it was shown that 15–30 injected melanoma cells already elicit an angiogenic response [6]
We investigated tumor angiogenesis in a genetic medaka fish melanoma model where the expression of a fish-specific oncogenic epidermal growth factor receptor (EGFR) leads to strong pro-tumorigenic signaling which is enhanced by autocrine loops [7, 8] and results in the malignant transformation of pigment cells and tumor development [9, 10]
Summary
Melanomas originate from cutaneous or extracutaneous melanocytes. In case of cutaneous melanoma, 25–35% of the tumors are derived from pre-existing nevi, the origin of the remaining tumors is unknown. By various oncogenic or epigenetic events, nevi can be stimulated to develop into the radial growth phase (RGP). At this stage, the pre-malignant cells expand in horizontal direction with restriction to the epidermis. Pro-angiogenic factors can already be secreted by RGP melanoma cells in vitro under appropriate conditions, such as the presence of fibroblasts [3] Because of their epidermal location, they are not able to attract blood vessels. In a xenotransplant model performed in zebrafishes which express eGFP under the flk promoter (with flk encoding Vegfr-2), it was shown that 15–30 injected melanoma cells already elicit an angiogenic response [6]. The authors used the strongly metastatic murine B16-F10 melanoma cells
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