Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34+ hematopoietic stem cells: Implications for ex vivo tumor purging and autologous stem cell transplantation

E. C. LaCasse, M. R. Bray, B. Patterson, W. M. Lim, S. Perampalam, L. G. Radvanyi, A. Keating, A. K. Stewart, R. Buckstein, J. S. Sandhu, N. Miller, D. Banerjee, D. Singh, A. R. Belch, L. M. Pilarski, J. Gariépy

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

The ribosome-inactivating protein, Shiga-like toxin-1 (SLT-1), targets cells that express the glycolipid globotriaosylceramide (CD77) on their surface. CD77 and/or SLT-1 binding was detected by flow cytometry and immunocytochemistry on lymphoma and breast cancer cells recovered from biopsies of primary human cancers as well as on B cells or plasma cells present in blood/bone marrow samples of multiple myeloma patients. Breast cancer cell lines also expressed receptors for the toxin and were sensitive to SLT-1. Treatment of primary B lymphoma, B-cell chronic lymphocytic leukemia, and myeloma B or plasma cells with SLT-1-depleted malignant B cells by 3- to 28-fold, as measured by flow cytometry. Depletion of myeloma plasma cells was confirmed using a cellular limiting dilution assay followed by reverse transcriptase-polymerase chain reaction analysis of clonotypic IgH transcripts, which showed a greater than 3 log reduction in clonotypic myeloma cells after SLT-1 treatment. Receptors for the toxin were not detected on human CD34+ hematopoietic progenitor cells (HPC). HPC were pretreated with a concentration of SLT-1 known to purge primary malignant B cells and cultured for 6 days. The number of HPC was comparable in toxin- treated and untreated cultures. HPC were functionally intact as well. Colony forming units (CFU) were present at an identical frequency in untreated and SLT-1 pretreated cultures, confirming that CFU escape SLT-1 toxicity. The results suggest the ex vivo use of SLT-1 in purging SLT-1 receptor-expressing malignant cells from autologous stem cell grafts of breast cancer, lymphoma, and myeloma patients.

Original languageEnglish (US)
Pages (from-to)2901-2910
Number of pages10
JournalBlood
Volume94
Issue number8
StatePublished - Oct 15 1999

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    LaCasse, E. C., Bray, M. R., Patterson, B., Lim, W. M., Perampalam, S., Radvanyi, L. G., Keating, A., Stewart, A. K., Buckstein, R., Sandhu, J. S., Miller, N., Banerjee, D., Singh, D., Belch, A. R., Pilarski, L. M., & Gariépy, J. (1999). Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34+ hematopoietic stem cells: Implications for ex vivo tumor purging and autologous stem cell transplantation. Blood, 94(8), 2901-2910.