Side population cells from human melanoma tumors reveal diverse mechanisms for chemoresistance

J Invest Dermatol. 2012 Oct;132(10):2440-2450. doi: 10.1038/jid.2012.161. Epub 2012 May 24.


Side population (SP) cells are identified as cells capable of excluding the fluorescent Hoechst dye and anticancer drugs, and it represents hematopoietic stem cells and chemoresistant cells from several solid tumors. In this study, we confirmed the presence of SP cells in tumors from melanoma patients. Melanoma SP cells overexpressed ATP-binding-cassette (ABC) transporters, ABCB1 and ABCB5. We generated a direct in vivo xenograft model, and demonstrated that SP cells were resistant to paclitaxel, a substrate of ABCB1, both in vitro and in vivo. However, melanoma SP cells were also resistant to temozolomide, which is not a substrate for ABC transporters, through IL-8 upregulation. In addition, gene profiling studies identified three signaling pathways (NF-κB, α6-β4-integrin, and IL-1) as differentially upregulated in melanoma SP cells, and there was a significant increase of PCDHB11 and decrease of FUK and TBX2 in these cells. Therefore, we provide evidence that SP is an enriched source of chemoresistant cells in human melanomas, and suggest that the selected genes and signaling pathways of SP cells may be a potential target for effective melanoma therapies. To our knowledge, this is a previously unreported study to isolate SP cells from melanoma patients and to investigate the gene expression profiling of these cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Coloring Agents
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Drug Resistance, Neoplasm / physiology*
  • Female
  • Humans
  • In Vitro Techniques
  • Interleukin-8 / physiology
  • Melanoma / drug therapy
  • Melanoma / pathology*
  • Melanoma / physiopathology*
  • Mice
  • Mice, Nude
  • Paclitaxel / therapeutic use
  • Side-Population Cells / pathology*
  • Side-Population Cells / physiology*
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / physiopathology*
  • Temozolomide
  • Up-Regulation / physiology
  • Xenograft Model Antitumor Assays


  • ABCB1 protein, human
  • ABCB5 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Coloring Agents
  • Interleukin-8
  • Dacarbazine
  • Paclitaxel
  • Temozolomide