Elsevier

Medical Hypotheses

Volume 49, Issue 2, August 1997, Pages 123-131
Medical Hypotheses

Thalidomide may impede cell migration in primates by down-regulating integrin β-chains: potential therapeutic utility in solid malignancies, proliferative retinopathy, inflammatory disorders, neointimal hyperplasia, and osteoporosis

https://doi.org/10.1016/S0306-9877(97)90217-6Get rights and content

Abstract

A growing number of human inflammatory disorders are reported to respond to treatment with thalidomide, and recently this drug has been shown to inhibit angiogenesis in the rabbit, in doses which can elicit teratogenicity in this species. Studies in marmosets and humans indicate that thalidomide, and a teratogenic analogue, decrease the expression of β integrin subunits, most notably β3 and the β2 produced by leukocytes. Since integrins are crucial for cell-matrix interactions, and the β2 integrins of leukocytes mediate adhesion to endothelium, it is reasonable to postulate that thalidomide inhibits cell migration in susceptible species, and that this accounts for its anti-inflammatory, anti-angiogenic, and teratogenic activity. This perspective suggests that thalidomide will show utility in the prevention or treatment of a wide range of disorders, including solid tumors, proliferative retinopathies, many inflammatory diseases, neointimal hyperplasia, and osteoporosis. It is likely that dietary fish oil — as well as selective inhibitors of urokinase, when and if they become clinically available — will complement the efficacy of thalidomide in most if not all of these applications.

References (108)

  • T. Darribère et al.

    The 140-kDa fibronectin receptor complex is required for mesodermal cell adhesion during gastrulation in the amphibian Pleurodeles waldii

    Devel Biol

    (1988)
  • E.T. Choi et al.

    Inhibition of neointimal hyperplasia by blocking αvβ3 integrin with a small peptide antagonist Gpen-GRGDSPCA

    J Vasc Surg

    (1994)
  • C.H. Blood et al.

    Tumor interactions with the vasculature: angiogenesis and tumor metastasis

    Biochim Biophys Acta

    (1990)
  • J. Folkman et al.

    Angiogenesis

    J Biol Chem

    (1992)
  • P.C. Brooks et al.

    Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels

    Cell

    (1994)
  • R.A. Swerlick et al.

    Expression and modulation of the vitronectin receptor on human dermal microvascular endothelial cells

    J Invest Dermatol

    (1992)
  • E. Ruoslahti et al.

    Anchorage dependence, integrins, and apoptosis

    Cell

    (1994)
  • J. Enenstein et al.

    Basic FGF and TGF-(3 differentially modulate integrin expression of human microvascular endothelial cells

    Exp Cell Res

    (1992)
  • A.D. Callow

    Current status of vascular grafts

    Surg Clin North Am

    (1982)
  • A. Miyauchi et al.

    Recognition of osteopontin and related peptides by an βvβ3 integrin stimulates immediate cell signals in osteoclasts

    J Biol Chem

    (1991)
  • M.E. Flores et al.

    RGD-directed attachment of isolated rat osteoclasts to osteopontin, bone sialoprotein, and fibronectin

    Exp Cell Research

    (1992)
  • R. Reich et al.

    Eicosapentaenoic acid reduces the invasive and metastatic activities of malignant tumor cells

    Biochem Biophys Res Commun

    (1989)
  • J.M. Connolly et al.

    Effects of fatty acids on invasion through reconstituted basement membrane (‘Matrigal’) by a human breast cancer cell line

    Cancer Lett

    (1993)
  • M.F. McCarty

    Fish oil may impede tumour angiogenesis and invasiveness by down-regulating protein kinase C and modulating eicosanoid production

    Med Hypotheses

    (1996)
  • E.S.R. Collie-Duguid et al.

    Inhibitory effect of fish oil n-3 poly-unsaturated fatty acids on the expression of endothelial cell adhesion molecules

    Biochem Biophys Res Commun

    (1996)
  • M.J. Tisdale

    Inhibition of lipolysis and muscle protein degradation by EPA in cancer cachexia

    Nutrition

    (1996)
  • S.J. Wigmore et al.

    The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer

    Nutrition

    (1996)
  • K. Sakaguchi et al.

    Eicospentaenoic acid inhibits bone loss due to ovariectomy in rats

    Prost Leuk Essent Fatty Acids

    (1994)
  • A.C. Buck et al.

    The protective role of eicosapentaenoic acid [EPA] in the pathogenesis of nephrolithiasis

    J Urol

    (1991)
  • P.J.N. Rothwell et al.

    Does fish oil benefit stone formers?

    J Urol

    (1993)
  • D. Moscatelli et al.

    Membrane and matrix localization of proteinases: a common theme in tumor cell invasion and angiogenesis

    Biochim Biophys Acta

    (1988)
  • P. Mignatti et al.

    Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade

    Cell

    (1986)
  • A. Estreicher et al.

    Characterization of the cellular binding site for the urokinase-type plasminogen activator

    J Biol Chem

    (1989)
  • L. Ossowski et al.

    Antibodies to plasminogen activator inhibit human tumor metastasis

    Cell

    (1983)
  • L. Ossowski

    Plasminogen activator dependent pathways in the dissemination of human tumor cells in the chick embryo

    Cell

    (1988)
  • J. Sheskin

    Thalidomide in the treatment of lepra reactions

    Clin Pharmacol Ther

    (1965)
  • R.C. Hastings

    Kellersberger Memorial lecture 1979: immunosuppressive/anti-inflammatory thalidomide analogues

    Ethiop Med J

    (1980)
  • S.S. Hendler et al.

    Thalidomide for autuimmune disease

    Med Hypotheses

    (1983)
  • E. Grosshans et al.

    Thalidomide therapy for inflammatory dermatoses

    Int J Dermatol

    (1984)
  • M. Samsoen et al.

    La thalidomide dans le traitement du lupus érythémateux chronique

    Ann Dermatol Venereol

    (1980)
  • J. Knop et al.

    Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosis

    Br J Dermatol

    (1983)
  • O. Gutierrez-Rodriguez et al.

    Treatment of refractory rheumatoid arthritis — the thalidomide experience

    J Rheumatol

    (1989)
  • F. Tamura et al.

    Combination thalidomide and cyclosporine for cardiac allograft rejection: Comparison with combination methylprednisolone and cyclosporine

    Transplantation

    (1990)
  • D. Heney et al.

    Thalidomide treatment for chronic graft-versus-host disease

    Br J Haematol

    (1991)
  • J. Ryan et al.

    Thalidomide to treat esophageal ulcer in AIDS

    N Engl J Med

    (1992)
  • G.B. Vogelsang et al.

    Thalidomide for the treatment of chronic graft-versus-host disease

    N Engl J Med

    (1992)
  • R.J. D'Amato et al.

    Thalidomide is an inhibitor of angiogenesis

  • R. Neubert et al.

    Thalidomide derivatives and the immune system. I: Changes in the pattern of integrin receptors and other surface markers on T lymphocyte subpopulations of marmoset blood

    Arch Toxicol

    (1993)
  • R. Neubert et al.

    Thalidomide and the immune system. 4: Down-regulation of the CD26 receptor, probably involved in the binding of HIV components to T cells in primates

    Life Sci

    (1995)
  • T.A. Springer

    Adhesion receptors of the immune system

    Nature

    (1990)
  • Cited by (0)

    View full text