Increased number of mast cells accompany enhanced collagen synthesis in linear localized scleroderma

1989 ◽  
Vol 281 (4) ◽  
pp. 288-290 ◽  
Author(s):  
K. Takeda ◽  
A. Hatamochi ◽  
H. Ueki
Keyword(s):  
Mast Cells ◽  
Collagen Synthesis ◽  
Localized Scleroderma ◽  
Linear Localized Scleroderma

Murine and Human NF1 Haploinsufficient Mast Cells Promote Alterations in Fibroblast Function and Organization of the Extracellular Matrix in Three-Dimensional Collagen Lattices and this Gain in Function Is Abrogated by the Addition of STI-571.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1465-1465
Author(s):  
Fengchun Yang ◽  
Clegg Travis ◽  
Shi Chen ◽  
Xiaohong Li ◽  
Selina A. Estwick ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Mast Cells ◽  
Tumor Microenvironment ◽  
Schwann Cells ◽  
Collagen Synthesis ◽  
Three Dimensional ◽  
Fibroblast Migration ◽  
Kit Ligand ◽  
Collagen Lattices

Abstract Cutaneous neurofibromas are a hallmark of neurofibromatosis type 1 (NF1), a common genetic disorder that is caused by mutations in the NF1 gene, which functions as a GAP for p21ras. Though the pathogenesis of neurofibroma formation is not completely known, haploinsufficiency of the nonneuronal lineages (fibroblasts, mast cells and endothelial cells) in the tumor microenvironment are required for neurofibroma formation (Zhu, Science 2002). These tumors are characterized by a high concentration of degranulating mast cells (MC) closely associated with fibroblasts, endothelial cells and Schwann cells. We have recently shown that Nf1−/− Schwann cells secrete kit-ligand to recruit Nf1+/− MCs to the tumor microenvironment via hyperactivation of a p21ras-PI3K-Rac dependent pathway (Yang, JCI 2003). Further, Nf1+/− MC also promote Schwann cell invasion and proliferation. Given that collagen is synthesized by fibroblasts and is approximately 80% of the weight of neurofibromas, we tested whether Nf1+/− MC promote the proliferation and collagen synthesis of fibroblasts. Strikingly, the proliferation of Nf1+/− fibroblasts in response to Nf1+/− MC conditioned media (MCCM) was 3 fold higher than any other group tested. In a wound healing assay Nf1+/− MCCM provided potent stimulus for the migration of Nf1+/− but not WT fibroblasts. Similarly, MCCM from primary human NF1+/− MC stimulated the proliferation, migration, and collagen synthesis of human NF1+/− fibroblasts, validating that our observations in Nf1+/− murine cells faithfully phenocopy the biology of human NF1 heterozygous cells. We next established three dimensional collagen lattices containing MC and fibroblasts of the respective genotypes to evaluate extracellular matrix (ECM) reorganization given that remodeling of the ECM by inflammatory cells promotes tumorigenesis. Histological examination revealed that while MC and fibroblasts of both genotypes localized to each other, there was a 2–3 fold quantitative increase in the localization or attachment of Nf1+/− MC to Nf1+/− fibroblasts. Further, Nf1+/− MC preferentially promoted a 2–3 fold increase in the lattice contraction indicative of alteration of the ECM in lattices containing either Nf1+/− or WT fibroblasts. Given that c-kit/kit-ligand interactions between MC and fibroblasts contribute to MC-fibroblast interactions, c-kit blocking antibodies or Gleevec, an antitumor drug that inhibits both BCR/ABL and c-kit tyrosine kinases, were added to MC-fibroblast cultures. Both of these agents blocked the activity of Nf1+/− MC on fibroblast proliferation, collagen remodeling and fibroblast migration. Collectively, these studies demonstrate that murine and human NF1 (Nf1) haploinsufficient MC stimulate the proliferation, migration, collagen synthesis of Nf1+/− fibroblasts as well as remodeling the ECM. This study provides strong evidence that Gleevec may be a candidate therapy for the treatment or prevention of neurofibromas.

scholarly journals 463 Absence of somatic mutations in linear localized scleroderma

2017 ◽  
Vol 137 (10) ◽  
pp. S271
Author(s):  
R. Higgins ◽  
A. Smith ◽  
R. Wälchli ◽  
M. Theiler ◽  
L. Weibel ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Localized Scleroderma ◽  
Linear Localized Scleroderma

scholarly journals 815 Genetic architecture of linear localized scleroderma

2018 ◽  
Vol 138 (5) ◽  
pp. S138
Author(s):  
R. Higgins ◽  
M. Theiler ◽  
A. Smith ◽  
R. Wälchli ◽  
L. Weibel ◽  
...  
Keyword(s):  
Genetic Architecture ◽  
Localized Scleroderma ◽  
Linear Localized Scleroderma

scholarly journals Adult-onset en coup de sabre scleroderma in a patient with linear localized scleroderma profunda: A case report and literature review

2021 ◽  
Vol 9 ◽  
pp. 2050313X2199330
Author(s):  
Roxana Mititelu ◽  
Zainab Ridha ◽  
Lydia Ouchene ◽  
Elena Netchiporouk
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Adult Patient ◽  
Localized Scleroderma ◽  
Adult Onset ◽  
Unique Case ◽  
Oral Methotrexate ◽  
Linear Scleroderma ◽  
Oral Steroids ◽  
Linear Localized Scleroderma

The en coup de sabre variant of linear scleroderma typically occurs in children. We report a unique case of adult-onset en coup de sabre scleroderma in a patient with linear localized scleroderma profunda. The patient was treated with oral steroids and oral methotrexate improving her cutaneous disease. This case highlights the importance of a thorough cutaneous examination as this adult patient developed an entity traditionally believed to occur in childhood.

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