Current concepts of metastasis in melanoma

Abstract

The main cause of death in melanoma patients is widespread metastases. Staging of melanoma is based on the primary tumor thickness, ulceration, lymph node and distant metastases. Metastases develop in regional lymph nodes, as satellite or in-transit lesions, or in distant organs. Lymph flow and chemotaxis is responsible for the homing of melanoma cells to different sites. Standard pathologic evaluation of sentinel lymph nodes fails to find occult melanoma in a significant proportion of cases. Detection of small numbers of malignant melanoma cells in these and other sites, such as adjacent to the primary site, bone marrow or the systemic circulation, may be enhanced by immunohistochemistry, reverse transcription PCR, evaluation of lymphatic vessel invasion and proteomics. In the organs to which melanoma cells metastasize, extravasation of melanoma cells is regulated by adhesion molecules, matrix metalloproteases, chemokines and growth factors. Melanoma cells may travel along external vessel lattices. After settling in the metastatic sites, melanoma cells develop mechanisms that protect them against the attack of the immune system. It †Author for correspondence Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, 930 Madison Avenue, Memphis, TN 38163, USA, Tel.: +1 901 448 6300, Fax: +1 901 448 6979, E-mail: aslominski@utmem.edu. Financial & competing interests disclosure:The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. is thought that one of the reasons why melanoma cells are especially resistant to killing is the fact that melanocytes (cells from which melanoma cells derive) are resistant to such noxious factors as ultraviolet light and reactive oxygen species. Targeted melanoma therapies are, so far, largely unsuccessful, and new ones, such as adjuvant inhibition of melanogenesis, are under development. NIH Public Access Keywordsbiotherapy; chemokine; integrin; melanoma; metastasis; sentinel lymph node Melanoma occurrence, staging & detectionBefore we review several concepts related to mechanisms of melanoma metastasis and treatment, we will briefly describe the currently available data about melanoma occurrence, the currently used system that divides melanoma patients into groups with different survival rates and the methods used to detect melanoma cells beyond the primary cutaneous tumor site. Since metastasis is the most important predictor of the patient's prognosis, there is a lot of effort directed at unequivocal determination of their presence in the adjacent epidermis, sentinel lymph nodes, circulation and distant sites (Box 1).Before melanoma cells metastasize they extend into the adjacent epidermis. 'Field cells' were characterized by Bastian et al. [3]. Epidermis adjacent to the acr...

Effect of Photodynamic Therapy in Melanoma Skin Cancer Cell Line A375: in vivo Study

“…Because melanoma is inherently resistant to radiotherapy. 6 Various chemotherapy, immunotherapy agents are used, but the overall success in metastatic melanoma is quite limited. 7 So further research is needed to evaluate new treatments for this fatal disease.…”

Signaling Pathways Altered During the Metastatic Progression of Melanoma

“…Cutaneous melanoma is the most aggressive type of skin cancer, and the high mortality rates worldwide caused by this disease is due to its great ability to form metastases and resist to current therapies [8,9,10]. Genetic and epigenetic alterations contribute to the development of cells able to invade and metastasize [11].…”

“…Genetic and epigenetic alterations contribute to the development of cells able to invade and metastasize [11]. These changes ensure the features that allow cells to modulate the microenvironment, and change their interactions with the extracellular matrix and other cells [8]. Although our knowledgement about the molecular pathogenesis of melanoma has increased, the molecular changes occuring during the malignant transformation of melanocytes are not very well described.…”

Circulating Melanoma Cells

“…Thus evasion from attack by natural killer (NK) cells affords melanoma cells a powerful means of protection from NK cell mediated cytotoxicity. Metastatic melanoma cells also develop resistance to inhibitory cytokines through the modification of oncostatin M receptors 60,61 . With such an arsenal of survival mechanisms, melanoma cells may indeed survive in the circulation for long periods of time.…”