Pulling RANK: Are Some Melanoma Cells More Malignant than Others?

Cellular heterogeneity is a frequently noted feature of melanoma. As reported in this issue, Kupas et al. identified heterogeneous expression of receptor activator of nuclear factor-κB (RANK) in melanoma cells in tumors and peripheral blood from patients. Increased expression of RANK was associated with the presence of metastatic disease and increased tumorigenicity in melanoma cells, raising the possibility that RANK signaling contributes to melanoma progression.     

Melanoma of the scalp: an underdiagnosed malignancy?

We report a case of scalp melanoma that was found incidentally after the patient complained of pruritic lesions on his scalp. The melanoma was 13 mm in diameter and had a Breslow thickness of 0.25 mm. The incidence of melanoma has been on the rise, with a high incidence occurring in men on the head, neck, and trunk. This case stresses the need to thoroughly examine the entire scalp when performing total body screening examinations for skin cancer.     

Combination Therapies for Melanoma: A New Standard of Care?

Recent data have demonstrated improved survival with targeted and immune therapies in patients with advanced melanoma, leading to much excitement amongst the oncology community and the widespread use of these drugs in combination regimens. However, the place of these combination therapies in the treatment of advanced melanoma remains to be fully determined. In this perspectives article, we critically review the available data and outline the rationale for these combinations being adopted as the standard of care for patients with advanced melanoma in the future.     

The Multidrug Transporter P-Glycoprotein: A Mediator of Melanoma Invasion?

Malignant melanoma shows high levels of intrinsic drug resistance associated with a highly invasive phenotype. In this study, we investigated the role of the drug transporter P-glycoprotein (Pgp) in the invasion potential of drug-sensitive (M14 WT, Pgp-negative) and drug-resistant (M14 ADR, Pgp-positive) human melanoma cells. Coimmunoprecipitation experiments assessed the association of Pgp with the adhesion molecule CD44 in multidrug resistant (MDR) melanoma cells, compared with parental ones. In MDR cells, the two proteins colocalized in the plasma membrane as visualized by confocal microscopy and immunoelectron microscopy on ultrathin cryosections. MDR melanoma cells displayed a more invasive phenotype compared with parental cells, as demonstrated by quantitative transwell chamber invasion assay. This was accomplished by a different migration strategy adopted by resistant cells ("chain collective") previously described in tumor cells with high metastatic capacity. The Pgp molecule, after stimulation with specific antibodies, appeared to cooperate with CD44, through the activation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) proteins. This activation led to an increase of metalloproteinase (MMP-2, MMP-3, and MMP-9) mRNAs, and proteolytic activities, which are associated with an increased invasive behavior. RNA interference experiments further demonstrated Pgp involvement in migration and invasion of resistant melanoma cells. A link was identified between MDR transporter Pgp, and MAPK signaling and invasion.