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Minor tumor infiltrating B cells opened a door to reveal and eliminate cancer initiating cells in metastatic melanomas
  1. Beatrix Kotlan1,5,
  2. Gabriella Liszkay2,
  3. Gyorgy Naszados3,
  4. Judit Olasz4,
  5. Szabolcs Horvath5,
  6. Vanda Plotar5,
  7. Andras Szollar6,
  8. Istvan Nagy Vamosi6,
  9. Akos Savolt6,
  10. Laszlo Toth6,
  11. Orsolya Csuka4,
  12. Maria Godeny3,
  13. Miklos Kasler7 and
  14. Francesco M Marincola8
  1. Aff1 grid.419617.c0000000106678064Molecular Immunology and ToxicologyNational Institute of Oncology Budapest Hungary
  2. Aff2 grid.419617.c0000000106678064OncodermatologyNational Institute of Oncology Budapest Hungary
  3. Aff3 grid.419617.c0000000106678064Radiological DiagnosticsNational Institute of Oncology Budapest Hungary
  4. Aff4 grid.419617.c0000000106678064PathogeneticsNational Institute of Oncology Budapest Hungary
  5. Aff5 grid.419617.c0000000106678064Surgical and Molecular TumorpathologyNational Institute of Oncology Budapest Hungary
  6. Aff6 grid.419617.c0000000106678064OncosurgeryNational Institute of Oncology Budapest Hungary
  7. Aff7 grid.419617.c0000000106678064Board of DirectorsNational Institute of Oncology Budapest Hungary
  8. Aff8 grid.467063.00000000403974222Research, Sidra Medical and Research Center Doha Qatar

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Meeting abstracts

Background

The theory and investigations on cancer stem cells (CSCs) have received growing attention, as these cells are responsible for the failure of cancer therapeutic strategies and the return of cancer.

Materials and methods

A complex tumorimmunological study on primary and metastatic cancerous tissue biopsies and peripheral blood of patients with malignant melanomas (n = 153) has been performed with ethical permission (ETT TUKEB 16462- 02/2010) and patients’ formal consent.

Results

We developed a methodology to select cancer initiating cells from fresh cancer cell cultures of malignant melanomas. Characteristic cell growth pattern, spheroid forming, CSC markers, like CD133, Nestin, ABCB5, CD20 and unique GD3 ganglioside expression were defined by immunofluorescence assay. Additionally tumor infiltrating B cells’ sialilated glycosphingolipid binding was defined by antibody phage display and immunglobulin repertoire analysis. Real Time PCR gene expression studies were done to reveal molecular parameters of regulatory mechanisms.

Conclusion

We provide here a novel strategy to detect cancer initiating cells in metastatic melanomas by double labeling with anti CD20 antibodies and sialilated glycosphingolipid antigen specific immunglobulins. With antibody engineering present findings might be turned into a novel cancer therapeutic approach targeting cancer stem cells.

Acknowledgments

Harry J. Lloyd Charitable Trust Melanoma Research Award/ 2010.