Expression of integrin receptors on 45 clinical neuroblastoma specimens

Immunohistological expression of integrins has been analyzed on 45 neuroblastoma specimens representative of the different clinical and histological forms of the tumor. None of the specimens expressed the α5 chain of the integrins. The β1 chain was expressed on all specimens, the α1 chain on 44 specimens and the α3 chain on 42; the 4 specimens which lacked α1 or α3 were stage‐4 neuroblastomas. The α2 chain was expressed on 18 specimens, and the α6 chain on 17;15 reacted with both. Their reactivity was related to the maturation of the tumor rather than the stage of the disease: they were expressed on lowgrade, well‐differentiated specimens; stage 3‐4 neuroblastoma specimens analyzed at diagnosis were negative, but usually expressed both chains when analyzed after in vivo differentiation by chemotherapy. αv reacted with 18 specimens and β3 with 12, without strict relation with the stage of the disease and/or its degree of differentiation; 9 well‐differentiated specimens expressed the β4 chain; only 4 well‐differentiated specimens expressed the α4 chain. The 4 specimens which lacked α1‐β1 or α3‐β1 expression had n‐myc amplification, whereas those which expressed either α4, β4, β3, or αv had no amplification. Furthermore, the expression of the 3 heterodimers α4‐β1, αv‐β3 and α6‐β4 was essentially observed on primary tumors which developed in the mediastinum. The expression of α2‐β1 and α6‐β1 was observed on both n‐myc‐positive and ‐negative specimens. β1 and α3, were diffusely expressed on all counterparts of these tumors, from undifferentiated neuroblasts to ganglion and Schwann cells. The α1 chain reacted with undifferentiated and intermediate neuroblasts as well as with Schwann cells, but ganglion cells were negative. α2 and α6 chains were negative on undifferentiated neuroblasts, variably expressed on intermediate neuroblasts, and restricted to Schwann cells in ganglioneuroma. The expression of α4 and β4 was restricted to Schwann cells. αv and β3 occasionally reacted with undifferentiated and intermediate neuroblasts; αv was strongly positive on Schwann cells but negative on ganglion cells, whereas β3 was positive on both neuronal and non‐neuronal populations.

[1]  E. Goillot,et al.  Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens , 1991, International journal of cancer.

[2]  D. Elder,et al.  Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. , 1990, Cancer research.

[3]  S. Kennel,et al.  Integrin (α6/β4) Expression in Human Lung Cancer as Monitored by Specific Monoclonal Antibodies , 1990 .

[4]  S. Albelda,et al.  Integrins and other cell adhesion molecules , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[5]  A. Sonnenberg,et al.  The alpha 1/beta 1 and alpha 6/beta 1 integrin heterodimers mediate cell attachment to distinct sites on laminin , 1990, The Journal of cell biology.

[6]  A. Sonnenberg,et al.  Integrin recognition of different cell-binding fragments of laminin (P1, E3, E8) and evidence that alpha 6 beta 1 but not alpha 6 beta 4 functions as a major receptor for fragment E8 , 1990, The Journal of cell biology.

[7]  S. Dedhar,et al.  Isolation of a novel integrin receptor mediating Arg-Gly-Asp-directed cell adhesion to fibronectin and type I collagen from human neuroblastoma cells. Association of a novel beta 1-related subunit with alpha v , 1990, The Journal of cell biology.

[8]  S. Bodary,et al.  The integrin beta 1 subunit associates with the vitronectin receptor alpha v subunit to form a novel vitronectin receptor in a human embryonic kidney cell line. , 1990, The Journal of biological chemistry.

[9]  E. Ruoslahti,et al.  A novel fibronectin receptor with an unexpected subunit composition (alpha v beta 1). , 1990, The Journal of biological chemistry.

[10]  W. Carter,et al.  The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells , 1990, Journal of Cell Biology.

[11]  F. Giancotti,et al.  Elevated levels of the α 5 β 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells , 1990, Cell.

[12]  R. Brentani,et al.  Independent prognostic value of laminin receptor expression in breast cancer survival. , 1990, Cancer research.

[13]  M. Elices,et al.  VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site , 1990, Cell.

[14]  J W Smith,et al.  Integrin (alpha v beta 3)-ligand interaction. Identification of a heterodimeric RGD binding site on the vitronectin receptor. , 1990, The Journal of biological chemistry.

[15]  S. Dedhar,et al.  Alterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes , 1990, The Journal of cell biology.

[16]  E. Ruoslahti,et al.  Alpha 2 beta 1 integrins from different cell types show different binding specificities. , 1990, The Journal of biological chemistry.

[17]  Richard O. Hynes,et al.  Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor α 4 β 1 , 1990, Cell.

[18]  M. Elices,et al.  The human integrin VLA-2 is a collagen receptor on some cells and a collagen/laminin receptor on others. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[19]  V. Combaret,et al.  Clinical value of N-myc oncogene amplification in 52 patients with neuroblastoma included in recent therapeutic protocols. , 1989, European journal of cancer & clinical oncology.

[20]  F. Walsh,et al.  Neural cell adhesion molecule (NCAM) is the antigen recognized by monoclonal antibodies of similar specificity in small‐cell lung carcinoma and neuroblastoma , 1989, International journal of cancer.

[21]  R. Warnke,et al.  Presence of cytoadhesins (IIb-IIIa-like glycoproteins) on human metastatic melanomas but not on benign melanocytes. , 1989, American journal of clinical pathology.

[22]  V. Combaret,et al.  Immunological detection of neuroblastoma cells in bone marrow harvested for autologous transplantation. , 1989, British Journal of Cancer.

[23]  A. Bernard,et al.  Suppressor effects and cyclic AMP accumulation by the CD29 molecule of CD4+ lymphocytes , 1989, Nature.

[24]  J. A. Mourik,et al.  Human vascular endothelial cells express a membrane protein complex immunochemically indistinguishable from the platelet VLA-2 (glycoprotein Ia-IIa) complex , 1989 .

[25]  R. Kramer,et al.  Identification of integrin collagen receptors on human melanoma cells. , 1989, The Journal of biological chemistry.

[26]  E. Ruoslahti,et al.  A neuroectoderm-associated ganglioside participates in fibronectin receptor-mediated adhesion of germinal cells to fibronectin. , 1989, Developmental biology.

[27]  R. Timpl,et al.  Domains of laminin with growth-factor activity , 1989, Cell.

[28]  A. Sonnenberg,et al.  Laminin receptor on platelets is the integrin VLA-6 , 1988, Nature.

[29]  C. R. Pinkerton,et al.  International criteria for diagnosis, staging and response to treatment in patients with neuroblastoma. , 1988, Progress in clinical and biological research.

[30]  W. Carter,et al.  Extracellular matrix receptors, ECMRII and ECMRI, for collagen and fibronectin correspond to VLA‐2 and VLA‐3 in the VLA family of heterodimers , 1988, Journal of cellular biochemistry.

[31]  M. Humphries,et al.  Neurite extension of chicken peripheral nervous system neurons on fibronectin: relative importance of specific adhesion sites in the central cell-binding domain and the alternatively spliced type III connecting segment , 1988, The Journal of cell biology.

[32]  D. Cheresh,et al.  Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. , 1987, The Journal of biological chemistry.

[33]  W. Carter,et al.  Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique alpha and common beta subunits , 1987, The Journal of cell biology.

[34]  T. Triche,et al.  Differentiation of human neuroblastoma recapitulates neural crest development. Study of morphology, neurotransmitter enzymes, and extracellular matrix proteins. , 1987, The American journal of pathology.

[35]  J. Strominger,et al.  Characterization of the cell surface heterodimer VLA-4 and related peptides. , 1987, The Journal of biological chemistry.

[36]  M. Hemler,et al.  The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. , 1987, The Journal of biological chemistry.

[37]  J. Zucker,et al.  High-dose chemoradiotherapy with bone marrow transplantation as consolidation treatment in neuroblastoma: an unselected group of stage IV patients over 1 year of age. , 1987, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  V. Woods,et al.  Very late activation antigens (VLA) are human leukocyte-neuronal crossreactive cell surface antigens , 1986, The Journal of experimental medicine.

[39]  T. Carey,et al.  Altered expression in squamous carcinoma cells of an orientation restricted epithelial antigen detected by monoclonal antibody A9. , 1986, Cancer research.

[40]  H. Sather,et al.  Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. , 1985, The New England journal of medicine.

[41]  E. Ruoslahti,et al.  Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor , 1985, Cell.

[42]  H. B. Marsden,et al.  Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age-linked classification of neuroblastomas. , 1984, Journal of the National Cancer Institute.

[43]  L. Hochholzer,et al.  Ganglioneuroblastoma of the posterior mediastinum: A clinicopathologic review of 80 cases , 1981, Cancer.

[44]  L. Culp,et al.  Requirement for two different cell-binding domains in fibronectin for neurite extension of neuronal derivative cells. , 1990, Journal of cell science.

[45]  R A Ross,et al.  Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. , 1989, Cancer research.