Angiogenesis Still Plays a Crucial Role in Human Melanoma Progression

Abstract

Angiogenesis plays a pivotal role in tumor progression, particularly in melanoma, the deadliest form of skin cancer. This review synthesizes current knowledge on the intricate interplay between angiogenesis and tumor microenvironment (TME) in melanoma progression. Pro-angiogenic factors, including VEGF, PlGF, FGF-2, IL-8, Ang, TGF-β, PDGF, integrins, MMPs, and PAF, modulate angiogenesis and contribute to melanoma metastasis. Additionally, cells within the TME, such as cancer-associated fibroblasts, mast cells, and melanoma-associated macrophages, influence tumor angiogenesis and progression. Anti-angiogenic therapies, while showing promise, face challenges such as drug resistance and tumor-induced activation of alternative angiogenic pathways. Rational combinations of anti-angiogenic agents and immunotherapies are being explored to overcome resistance. Biomarker identification for treatment response remains crucial for personalized therapies. This review highlights the complexity of angiogenesis in melanoma and underscores the need for innovative therapeutic approaches tailored to the dynamic TME.

Keywords: angiogenesis; anti-angiogenesis; melanoma; metastasis; tumor progression.

Figure 1

Overview of the molecules involved in angiogenesis in melanoma.

Figure 2

(A) Photomicrographs of an example of invasive malignant melanoma with a high density of macrophages (highlighted by brown chromogen) within the tumor sheets (immunohistochemistry for CD163, original magnification 4×). (B) Scanning magnification of CD163+ macrophages associated with malignant melanoma (immunohistochemistry for CD163, original magnification 10×).