The Impact of Hyaluronan on Tumor Progression in Cutaneous Melanoma

Abstract

The incidence of cutaneous melanoma is rapidly increasing worldwide. Cutaneous melanoma is an aggressive type of skin cancer, which originates from malignant transformation of pigment producing melanocytes. The main risk factor for melanoma is ultraviolet (UV) radiation, and thus it often arises from highly sun-exposed skin areas and is characterized by a high mutational burden. In addition to melanoma-associated mutations such as BRAF, NRAS, PTEN and cell cycle regulators, the expansion of melanoma is affected by the extracellular matrix surrounding the tumor together with immune cells. In the early phases of the disease, hyaluronan is the major matrix component in cutaneous melanoma microenvironment. It is a high-molecular weight polysaccharide involved in several physiological and pathological processes. Hyaluronan is involved in the inflammatory reactions associated with UV radiation but its role in melanomagenesis is still unclear. Although abundant hyaluronan surrounds epidermal and dermal cells in normal skin and benign nevi, its content is further elevated in dysplastic lesions and local tumors. At this stage hyaluronan matrix may act as a protective barrier against melanoma progression, or alternatively against immune cell attack. While in advanced melanoma, the content of hyaluronan decreases due to altered synthesis and degradation, and this correlates with poor prognosis. This review focuses on hyaluronan matrix in cutaneous melanoma and how the changes in hyaluronan metabolism affect the progression of melanoma.

M1 Macrophages Induce Protumor Inflammation in Melanoma Cells through TNFR–NF-κB Signaling

“…Similar structures were not found in M0 or M2 CM-exposed cells. Previous studies have shown a protective role of pericellular HA against extrinsic factors, such as UVR and chemotherapeutic drugs (Ha sova ´et al, 2011;Takabe et al, 2022;Va ´radi et al, 2012). In melanocytes, the pericellular HA coat has been shown to protect against UVB-induced inflammatory responses (Takabe et al, 2019).…”

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies

“…In addition, platelet-derived growth factor β and transforming growth factor have been found to be the only growth factors that have been shown to prevent the mesothelioma growth. Despite the reality that various growth factors and even their receptors play a role in the dissemination of mesothelioma ( 25 ).…”

Effects of Hyaluronan on Breast Cancer Aggressiveness

“…Among all the matrix components, HA is one of the most deregulated in human malignancies, and its amount in the tumor stroma affects overall survival and outcome [37][38][39]. High levels of HA are observed in several tumors compared to healthy tissues, such as renal [40], hepatocellular [41], head and neck [42] and lung squamous cell carcinomas [43], lymphoma [44], glioma [45], prostate [46], melanoma [47], breast [48], and ovarian [49] cancers. In most cancer cases, stromal accumulation of HA strongly correlates with an unfavorable prognosis and decreased survival probability [37,49,50].…”