Drs. Claire Lugassy and Raymond Barnhill are respectively Research Associate Professor and Professor of Pathology in the Department of Pathology and Laboratory Medicine led by Dr. Jonathan Braun at UCLA. This new study published in Nature (March 6 2014) is based on the innovative melanoma metastasis research field of angiotropism and extravascular migratory metastasis (EVMM) in melanoma (and other tumors) opened by Lugassy and Barnhill about 15 years ago. During EVMM, tumor cells migrate in a crawling manner along the external surfaces of vascular channels, without intravasation, demonstrating angiotropism and pericytic mimicry. It is a revolutionary new paradigm about the mechanisms of melanoma (and other malignant solid tumors) metastasis, additional to the extensively studied intravascular dissemination of tumor cells.
This new study in Nature, based on this research field and in collaboration with a German team lead by Dr. Thomas Tueting, reports that repetitive UV exposure of primary cutaneous melanomas in a genetically engineered mouse model promotes metastatic progression through angiotropism, enhancing the spreading of tumor cells along abluminal blood vessel surfaces, and increasing the number of lung metastases. The UV-induced neutrophilic inflammatory response stimulated angiogenesis and promoted the ability of melanoma cells to migrate towards endothelial cells and use selective motility cues on their surfaces, i.e. pericytic mimicry and EVMM. The results not only reveal how UV irradiation of epidermal keratinocytes is sensed by the innate immune system, but also show that the resulting inflammatory response catalyses reciprocal melanoma-endothelial cell interactions leading to angiotropism, pericytic mimicry, and EVMM. This new study strongly supports the concepts and works of Lugassy and Barnhill on extravascular melanoma metastasis, and confirms that targeting this specific association between melanoma cells and the endothelium endothelial cells represent a rational strategy to specifically interfere with metastatic progression.
Bald T, Quast T, Landsberg J, Rogava M, Glodde N, Lopez-Ramos D, Kohlmeyer J, Riesenberg S, van den Boorn-Konijnenberg D, Hömig-Hölzel C, Reuten R, Schadow B, Weighardt H, Wenzel D, Helfrich I, Schadendorf D, Bloch W, Bianchi ME, Lugassy C, Barnhill RL, Koch M, Fleischmann BK, Förster I, Kastenmüller W, Kolanus W, Hölzel M, Gaffal E, Tüting T. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature. 2014 Feb 26. doi: 10.1038/nature13111. [Epub ahead of print] PubMed PMID: 24572365.