Multiple Sclerosis Treatment and Melanoma Development

Int J Mol Sci. 2020 Apr 22;21(8):2950. doi: 10.3390/ijms21082950.

Abstract

Therapy of multiple sclerosis (MS) with disease-modifying agents such as natalizumab or fingolimod has been associated with the development of cutaneous melanoma. Here we briefly revise literature data and report of a case of a 48-year old woman who developed a melanoma and several atypical naevi after sub sequential treatment with natalizumab (1 year) and fingolimod (7 years). By immunohistochemistry we observed the presence of T cells and leukocyte infiltration as well as of vascular endothelial growth factor (VEGF)-A expression in the patient melanoma biopsy. Then, we analyzed proliferation, migration and VEGF-A expression in three melanoma cell lines and found out that both natalizumab and fingolimod inhibited tumor cell proliferation but promoted or blocked cell migration depending on the cell line examined. VEGF-A secretion was augmented in one melanoma cell line only after fingolimod treatment. In conclusion, our in vitro data do not support the hypothesis of a direct action of natalizumab or fingolimod on melanoma progression but acting on the tumor microenvironment these treatments could indirectly favor melanoma evolution.

Keywords: VEGF-A; fingolimod; melanoma; natalizumab.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Biomarkers
  • Biopsy
  • Disease Susceptibility
  • Female
  • Fingolimod Hydrochloride / adverse effects
  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Immunohistochemistry
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Melanoma / diagnosis*
  • Melanoma / etiology*
  • Melanoma / metabolism
  • Melanoma / therapy
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Multiple Sclerosis / complications*
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / therapy*
  • Natalizumab / adverse effects
  • Natalizumab / therapeutic use
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / etiology
  • Skin Neoplasms / therapy
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Immunosuppressive Agents
  • Natalizumab
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fingolimod Hydrochloride