Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells

E. K. Neely, Ronald (Ron) Rosenfeld, A. Illescas, S. D. Smith

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125l-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II ≫ insulin, 125I-IGF-II was displaced by IGF-II ≫ insulin = IGF-I, and 125I-insulin was displaced by insulin ≫ IGF-II ≫ IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.

Original languageEnglish (US)
Pages (from-to)1134-1142
Number of pages9
JournalLeukemia
Volume6
Issue number11
StatePublished - Nov 1992
Externally publishedYes

Fingerprint

B-Lymphoid Precursor Cells
Insulin-Like Growth Factor I
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Insulin-Like Growth Factor II
Insulin
Competitive Binding
Insulin Receptor
Cell Proliferation
Peptides
Cell Membrane
IGF Type 2 Receptor
Insulin Antibodies
Cell Line
Insulin-Like Growth Factor Binding Proteins
IGF Type 1 Receptor

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Neely, E. K., Rosenfeld, R. R., Illescas, A., & Smith, S. D. (1992). Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells. Leukemia, 6(11), 1134-1142.

Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells. / Neely, E. K.; Rosenfeld, Ronald (Ron); Illescas, A.; Smith, S. D.

In: Leukemia, Vol. 6, No. 11, 11.1992, p. 1134-1142.

Research output: Contribution to journalArticle

Neely, EK, Rosenfeld, RR, Illescas, A & Smith, SD 1992, 'Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells', Leukemia, vol. 6, no. 11, pp. 1134-1142.
Neely EK, Rosenfeld RR, Illescas A, Smith SD. Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells. Leukemia. 1992 Nov;6(11):1134-1142.
Neely, E. K. ; Rosenfeld, Ronald (Ron) ; Illescas, A. ; Smith, S. D. / Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells. In: Leukemia. 1992 ; Vol. 6, No. 11. pp. 1134-1142.
@article{4a0b2bde399941d0814183933dfbfcc3,
title = "Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells",
abstract = "Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125l-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6{\%}, 7.1{\%}, and 4.3{\%} of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II ≫ insulin, 125I-IGF-II was displaced by IGF-II ≫ insulin = IGF-I, and 125I-insulin was displaced by insulin ≫ IGF-II ≫ IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130{\%} increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.",
author = "Neely, {E. K.} and Rosenfeld, {Ronald (Ron)} and A. Illescas and Smith, {S. D.}",
year = "1992",
month = "11",
language = "English (US)",
volume = "6",
pages = "1134--1142",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells

AU - Neely, E. K.

AU - Rosenfeld, Ronald (Ron)

AU - Illescas, A.

AU - Smith, S. D.

PY - 1992/11

Y1 - 1992/11

N2 - Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125l-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II ≫ insulin, 125I-IGF-II was displaced by IGF-II ≫ insulin = IGF-I, and 125I-insulin was displaced by insulin ≫ IGF-II ≫ IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.

AB - Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125l-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II ≫ insulin, 125I-IGF-II was displaced by IGF-II ≫ insulin = IGF-I, and 125I-insulin was displaced by insulin ≫ IGF-II ≫ IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.

UR - http://www.scopus.com/inward/record.url?scp=0026566913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026566913&partnerID=8YFLogxK

M3 - Article

VL - 6

SP - 1134

EP - 1142

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 11

ER -