bims-meladi 2021-05-16 papers

Issue of 2021‒05‒16
three papers selected by
Farah Jaber-Hijazi
University of the West of Scotland

Gan To Kagaku Ryoho. 2021 Apr;48(4): 499

[Melanoma and Non‒Melanoma Skin Cancers].

Nat Commun. 2021 May 12. 12(1): 2742

Ultraviolet light-induced collagen degradation inhibits melanoma invasion.

Timothy Budden, Caroline Gaudy-Marqueste, Andrew Porter, Emily Kay, Shilpa Gurung, Charles H Earnshaw, Katharina Roeck, Sarah Craig, Víctor Traves, Jean Krutmann, Patricia Muller, Luisa Motta, Sara Zanivan, Angeliki Malliri, Simon J Furney, Eduardo Nagore, Amaya Virós.

Ultraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.

DOI: https://doi.org/10.1038/s41467-021-22953-z

J Exp Clin Cancer Res. 2021 May 08. 40(1): 159

Hypoxia-dependent drivers of melanoma progression.

Simona D'Aguanno, Fabiana Mallone, Marco Marenco, Donatella Del Bufalo, Antonietta Moramarco.

Hypoxia, a condition of low oxygen availability, is a hallmark of tumour microenvironment and promotes cancer progression and resistance to therapy. Many studies reported the essential role of hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry and response to therapy in melanoma. Melanoma is an aggressive cancer originating from melanocytes located in the skin (cutaneous melanoma), in the uveal tract of the eye (uveal melanoma) or in mucosal membranes (mucosal melanoma). These three subtypes of melanoma represent distinct neoplasms in terms of biology, epidemiology, aetiology, molecular profile and clinical features.In this review, the latest progress in hypoxia-regulated pathways involved in the development and progression of all melanoma subtypes were discussed. We also summarized current knowledge on preclinical studies with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis or vasculogenic mimicry. Finally, we described available evidence on clinical studies investigating the use of Hypoxia-Inducible Factor-1 inhibitors or antiangiogenic drugs, alone or in combination with other strategies, in metastatic and adjuvant settings of cutaneous, uveal and mucosal melanoma.Hypoxia-Inducible Factor-independent pathways have been also reported to regulate melanoma progression, but this issue is beyond the scope of this review.As evident from the numerous studies discussed in this review, the increasing knowledge of hypoxia-regulated pathways in melanoma progression and the promising results obtained from novel antiangiogenic therapies, could offer new perspectives in clinical practice in order to improve survival outcomes of melanoma patients.

Keywords: Angiogenesis; Cutaneous melanoma (CM); HIF-1; Hypoxia; Mucosal melanoma (MM); Uveal melanoma (UM); Vasculogenic mimicry

DOI: https://doi.org/10.1186/s13046-021-01926-6