Characterization of Mast Cells Residing in Cutaneous Neurofibromas

Kamide, Ryoichi; Nomura, Naohiro; Niimura, Michihito

doi:10.1159/000248467

Cited by 13 publications

(10 citation statements)

References 4 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we compared the level of mast cell infiltration in neurofibroma tumor tissues with various Scf statuses by toluidine blue staining. We found that mouse neurofibroma tumors with normal Scf expression showed high levels of mast cell infiltration ( Figure 4A), in line with the human neurofibroma pathological signatures (11)(12)(13)(14). Strikingly, we found that mast cell density in neurofibroma is correlated to SCF expression in Schwann cells.…”

Section: Scf Expression In Normal and Neoplastic Schwann Cells In Vivosupporting

confidence: 77%

“…Neurofibromas are heterogeneous tumors comprised of neoplastic Schwann cells and nonneoplastic fibroblasts, vascular endothelial cells, and mast cells, as well as dense collagen. The presence of mast cell infiltration can be frequently observed in neurofibromas (11)(12)(13)(14); however, it is not common in other types of neoplasms. The neurofibroma-associated mast cells appear to be at activated status, as levels of local histamine content (13) and circulating serum IgE are high (15).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis

Liao

Booker

Brosseau

et al. 2018

Journal of Clinical Investigation

116

View full text Add to dashboard Cite

Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.

show abstract

Section: Scf Expression In Normal and Neoplastic Schwann Cells In Vivosupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis

Liao

Booker

Brosseau

et al. 2018

Journal of Clinical Investigation

116

View full text Add to dashboard Cite

show abstract

“…Concerning neurofibromas there had been former publications with quantifications of mast cells [23,24] but without further differentiation. The mast cell density in normal skin of NF patients had not yet been examined.…”

Section: Discussionmentioning

confidence: 99%

Semiquantitative Aspects of Mast Cells in Normal Skin and in Neurofibromas of Neurofibromatosis Types 1 and 5

Nürnberger

Moll²

1994

Dermatology

View full text Add to dashboard Cite

Mast cells are supposed to influence the growth of neurofibromas, because some of their mediators may also act as growth factors. Accordingly, mast cell stabilizers are claimed to reduce proliferation and itching of neurofibromas. Therefore, we quantified the mast cells of 19 neurofibromas and compared them with normal skin. We saw a statistically significant increase in mast cells in neurofibromas versus normal skin. However, there is no correlation between the age of neurofibromatosis (NF) patients and mast cell density. In our study the density of mast cells in neurofibromas is also independent of NF type, age of neurofibroma and chronic ultraviolet exposure in contrast to normal skin. Different tumors of the same patient had similar mast cell counts.

show abstract

“…It is hypothesized that mast cells and components released from their degranulation are a major cause of pruritus, as mast cells are well-known to be present in the cNF microenvironment and may contribute to tumor initiation, progression, and angiogenesis. [31][32][33][34][35][36] However, it is also possible that pruritus is a manifestation of a neuropathy affecting the small nerve tributaries in the skin, which are integral to the development of these tumors. 30,37 Indeed, anecdotally, people with NF1 report improvement in pruritus after therapy with antineuropathic agents such as gabapentin or mast cell stabilizing agents such as ketotifen, indicating that both mechanisms may be active.…”

Section: Cutaneous Neurofibromas: Clinical Definitions or Descriptorsmentioning

confidence: 99%

Cutaneous neurofibromas

et al. 2018

View full text Add to dashboard Cite

The development of effective therapies for cNF requires formulation of diagnostic criteria that encompass the clinical and histologic features of these tumors. However, there are several areas of overlap between cNF and other neurofibromas that make distinctions between cutaneous and other neurofibromas more difficult, requiring careful deliberation with input across the multiple disciplines that encounter these tumors and ultimately, prospective validation. The ultimate goal of this work is to facilitate accurate diagnosis and meaningful therapeutics for cNF.

show abstract

Characterization of Mast Cells Residing in Cutaneous Neurofibromas

Cited by 13 publications

References 4 publications

Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis

Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis

Semiquantitative Aspects of Mast Cells in Normal Skin and in Neurofibromas of Neurofibromatosis Types 1 and 5

Cutaneous neurofibromas

Contact Info

Product

Resources

About