Role of the Skin Microenvironment in Melanomagenesis: Epidermal Keratinocytes and Dermal Fibroblasts Promote BRAF Oncogene-Induced Senescence Escape in Melanocytes.

BRAFV600E is the most common mutation driver in melanoma. This mutation is known to cause a brief burst of proliferation followed by growth arrest and senescence, which prevent an uncontrolled cell proliferation. This phenomenon is known as oncogene-induced senescence (OIS) and OIS escape is thought to lead to melanomagenesis. Much attention has been focused on the melanocyte-intrinsic mechanisms that contribute to senescence escape. Additional genetic events such as the loss of tumor suppressor PTEN and/or epigenetic changes that contribute to senescence escape have been described. However, the role of the skin microenvironment-specifically, the role of epidermal keratinocytes-on melanomagenesis is not fully understood. In this study, we employ a microfluidic platform to study the interaction between melanocytes expressing the BRAFV600E mutation as well as keratinocytes and dermal fibroblasts. We demonstrate that keratinocytes suppress senescence-related genes and promote the proliferation of transformed melanocytes. We also show that a keratinocyte-conditioned medium can alter the secretion of both pro- and anti-tumorigenic factors by transformed melanocytes. In addition, we show that melanocytes and keratinocytes from donors of white European and black African ancestry display different crosstalks; i.e., white keratinocytes appear to promote a more pro-tumorigenic phenotype compared with black keratinocytes. These data suggest that keratinocytes exert their influence on melanomagenesis both by suppressing senescence-related genes in melanocytes and by affecting the balance of the melanocyte-secreted factors that favor tumorigenesis.

A Case of Linear Cutaneous Lupus Erythematosus in a 55-Year-Old Woman.

BACKGROUND Linear cutaneous lupus erythematosus (LCLE) is uncommon and occurs mainly in children and young adults. To our knowledge, only ten cases of LCLE in adults have been previously reported. A case is presented of LCLE of the left arm in a 55-year-old woman. CASE REPORT A 55-year-old Caucasian woman from the Midwestern United States presented with a three-month history of a pruritic linear eruption on the left arm. She had a previous history of methicillin-resistant Staphylococcus aureus (MRSA) infection of the left forearm. She had previously been treated with topical triamcinolone, hydrocortisone cream, hydroxyzine, and two courses of prednisone. Physical examination showed a unilateral and linear erythematous skin lesion of the left arm that contained papules and followed the embryonal developmental epidermal lines of Blaschko. Histopathology of a 4 mm skin punch biopsy showed an interface dermatitis with keratinocyte necrosis and increased dermal mucin. Immunofluorescence of the skin biopsy, including for antinuclear antigen (ANA), was negative. Prednisone treatment reduced the symptoms of pruritis but did not resolve the rash. However, following topical treatment with betamethasone dipropionate cream for between two and three weeks, and the use of sunblock, the skin lesions resolved. CONCLUSIONS This rare case of LCLE in an older adult showed a similar response to treatment as other forms of cutaneous lupus erythematosus, with treatment that included topical steroids and sun protection. Also, this case supports that environmental trigger factors, such as prior infections, might provide insights into the etiology of LCLE.