Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models
Jeffrey E. DeClue, Sue Heffelfinger, Giovanna Benvenuto, Bo Ling, Shaowei Li, Wen Rui, William C. Vass, David Viskochil, Nancy Ratner
Jeffrey E. DeClue, Sue Heffelfinger, Giovanna Benvenuto, Bo Ling, Shaowei Li, Wen Rui, William C. Vass, David Viskochil, Nancy Ratner
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Epidermal growth factor receptor expression in neurofibromatosis type 1–related tumors and NF1 animal models

Abstract

We have found that EGF-R expression is associated with the development of the Schwann cell–derived tumors characteristic of neurofibromatosis type 1 (NF1) and in animal models of this disease. This is surprising, because Schwann cells normally lack EGF-R and respond to ligands other than EGF. Nevertheless, immunoblotting, Northern analysis, and immunohistochemistry revealed that each of 3 malignant peripheral nerve sheath tumor (MPNST) cell lines from NF1 patients expressed the EGF-R, as did 7 of 7 other primary MPNSTs, a non-NF1 MPNST cell line, and the S100+ cells from each of 9 benign neurofibromas. Furthermore, transformed derivatives of Schwann cells from NF1–/– mouse embryos also expressed the EGF-R. All of the cells or cell lines expressing EGF-R responded to EGF by activation of downstream signaling pathways. Thus, EGF-R expression may play an important role in NF1 tumorigenesis and Schwann cell transformation. Consistent with this hypothesis, growth of NF1 MPNST lines and the transformed NF1–/– mouse embryo Schwann cells was greatly stimulated by EGF in vitro and could be blocked by agents that antagonize EGF-R function.

Authors

Jeffrey E. DeClue, Sue Heffelfinger, Giovanna Benvenuto, Bo Ling, Shaowei Li, Wen Rui, William C. Vass, David Viskochil, Nancy Ratner

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EGF-R expression in NF1 tumor sections. Paraffin sections were stained w...
EGF-R expression in NF1 tumor sections. Paraffin sections were stained with anti–EGF-R (b, d, and f) or anti-S100 (a, c, and e) or with both antibodies (g, h, and i). Visualization of single antibodies was with 3′3-diaminobenzidine HCl (DAB; brown) (a–f). Double labeling used nitroblue tetrazolium (NBT/BCIP; blue) for anti-S100, and DAB (brown) for anti–EGF-R (g–i). In a, b, and d–f, the counterstain is hematoxylin (blue); in c and g–i, the counterstain is nuclear fast red (pink). (a–d) Sections from MPNST. In a, the arrow points to a normal nerve within the tumor, containing S100+ cells, whereas the tumor matrix is S100–. An adjacent section from the same tumor in b shows that most cells are EGF-R+. Another MPNST contains S100+ cells (c) and is mostly negative for EGF-R (d). (e and f) Sections of normal human nerve (arrow points to perineurium). (g) A section of a cutaneous neurofibroma with EGF-R+/S100+ cells. (h) A section from a dissociated neurofibroma cell preparation. The arrow designates a group of cells double stained by anti-S100 and anti–EGF-R. (i) A section from a dissociated normal nerve preparation. No double-labeled cells are detected. a–g, bar: 34.2 μm; h and i, bar: 16.3 μm.