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, Alexander Keith 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

65 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Shiga Toxin 1
Shiga Toxins
Purging
Stem Cell Transplantation
Hematopoietic Stem Cells
Stem cells
Tumors
Lymphoma
Breast Neoplasms
Cells
Neoplasms
B-Lymphocytes
Stem Cells
Flow cytometry
Plasma Cells
Multiple Myeloma
Plasmas
Flow Cytometry
Ribosome Inactivating Proteins
Shiga-like toxin receptor

ASJC Scopus subject areas

  • Hematology

Cite this

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

In: Blood, Vol. 94, No. 8, 15.10.1999, p. 2901-2910.

Research output: Contribution to journalArticle

LaCasse, EC, Bray, MR, Patterson, B, Lim, WM, Perampalam, S, Radvanyi, LG, Keating, A, Stewart, AK, Buckstein, R, Sandhu, JS, Miller, N, Banerjee, D, Singh, D, Belch, AR, Pilarski, LM & 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, vol. 94, no. 8, pp. 2901-2910.
LaCasse, E. C. ; Bray, M. R. ; Patterson, B. ; Lim, W. M. ; Perampalam, S. ; Radvanyi, L. G. ; Keating, A. ; Stewart, Alexander Keith ; Buckstein, R. ; Sandhu, J. S. ; Miller, N. ; Banerjee, D. ; Singh, D. ; Belch, A. R. ; Pilarski, L. M. ; Gariépy, J. / 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. In: Blood. 1999 ; Vol. 94, No. 8. pp. 2901-2910.
@article{9a207cce3f5c46d6a5671ad65b3cc406,
title = "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",
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.",
author = "LaCasse, {E. C.} and Bray, {M. R.} and B. Patterson and Lim, {W. M.} and S. Perampalam and Radvanyi, {L. G.} and A. Keating and Stewart, {Alexander Keith} and R. Buckstein and Sandhu, {J. S.} and N. Miller and D. Banerjee and D. Singh and Belch, {A. R.} and Pilarski, {L. M.} and J. Gari{\'e}py",
year = "1999",
month = "10",
day = "15",
language = "English (US)",
volume = "94",
pages = "2901--2910",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "8",

}

TY - JOUR

T1 - Shiga-like toxin-1 receptor on human breast cancer, lymphoma, and myeloma and absence from CD34+ hematopoietic stem cells

T2 - Implications for ex vivo tumor purging and autologous stem cell transplantation

AU - LaCasse, E. C.

AU - Bray, M. R.

AU - Patterson, B.

AU - Lim, W. M.

AU - Perampalam, S.

AU - Radvanyi, L. G.

AU - Keating, A.

AU - Stewart, Alexander Keith

AU - Buckstein, R.

AU - Sandhu, J. S.

AU - Miller, N.

AU - Banerjee, D.

AU - Singh, D.

AU - Belch, A. R.

AU - Pilarski, L. M.

AU - Gariépy, J.

PY - 1999/10/15

Y1 - 1999/10/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=13044254786&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13044254786&partnerID=8YFLogxK

M3 - Article

VL - 94

SP - 2901

EP - 2910

JO - Blood

JF - Blood

SN - 0006-4971

IS - 8

ER -