Cutaneous malignant melanoma: Correlation between neovascularization and peritumor accumulation of mast cells overexpressing vascular endothelial growth factor

th, Tibor T; th-Jakatics, Ria T; Jimi, Shiro; Takebayashi, Shigeo; Kawamoto, Noriko

doi:10.1053/hupa.2000.16658

Cited by 140 publications

(35 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, although these previous efforts support a role of MCs in melanoma, the mechanisms by which MCs impact on this type of pathology are not fully understood. One favored scenario though is that MCs might contribute by expressing pro-angiogenic factors such as VEGF [16], bFGF [35] and histamine [36], whereas other studies have suggested that MCs may account for TIM-3-mediated immunosuppression [37]. …”

Section: Discussionmentioning

confidence: 99%

The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung

et al. 2017

View full text Add to dashboard Cite

Mast cell secretory granules are densely packed with various bioactive mediators including proteases of chymase, tryptase and CPA3 type. Previous studies have indicated that mast cells can affect the outcome of melanoma but the contribution of the mast cell granule proteases to such effects has not been clear. Here we addressed this issue by assessing mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3 (Cpa3), as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung. Although mice with individual deficiency in the respective proteases did not differ significantly from wildtype mice in the extent of melanoma colonization, mice with multiple protease deficiency (Mcpt4/Mcpt6/Cpa3-deficient) exhibited a higher extent of melanoma colonization in lungs as compared to wildtype animals. This was supported by higher expression of melanoma-specific genes in lungs of Mcpt4/Mcpt6/CPA3-deficient vs. wildtype mice. Cytokine profiling showed that the levels of CXCL16, a chemokine with effects on T cell populations and NKT cells, were significantly lower in lungs of Mcpt4/Mcpt6/Cpa3-deficient animals vs. controls, suggesting that multiple mast cell protease deficiency might affect T cell or NKT cell populations. In line with this, we found that the Mcpt4/Mcpt6/Cpa3-deficiency was associated with a reduction in cells expressing CD1d, a MHC class 1-like molecule that is crucial for presenting antigen to invariant NKT (iNKT) cells. Together, these findings indicate a protective role of mast cell-specific proteases in melanoma dissemination, and suggest that this effect involves a CXCL16/CD1d/NKT cell axis.

show abstract

Section: Discussionmentioning

confidence: 99%

The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Accordingly, strong VEGF-A expression is observed in the more aggressive and potentially metastasizing squamous cell carcinoma and melanoma. [29], [31] …”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Analysis of the Mechanistic Target of Rapamycin and Hypoxia Signalling Pathways in Basal Cell Carcinoma and Trichoepithelioma

et al. 2014

View full text Add to dashboard Cite

BackgroundBasal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways.ObjectivesTo determine whether HIF1/mTOR signalling is involved in BCC and TE.MethodsWe used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, <30%, 30–80% and >80%).ResultsAmong 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1α), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included.ConclusionsHIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

show abstract

“…In addition, we have found that VEGFs are chemotactic for mast cells (59), indicating that mast cells are a target, in addition to be a source, for VEGFs (132). Several studies have highlighted the association and/or the correlation in human tumors between increased mast cell density and angiogenesis by evaluating the expression of the proangiogenic isoform VEGF-A (42, 45, 70, 80, 96, 123). …”

Section: Role Of Tamcs In Tumor Angiogenesis and Lymphangiogenesismentioning

confidence: 99%

Are Mast Cells MASTers in Cancer?

et al. 2017

View full text Add to dashboard Cite

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin’s lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.

show abstract

Cutaneous malignant melanoma: Correlation between neovascularization and peritumor accumulation of mast cells overexpressing vascular endothelial growth factor

Cited by 140 publications

References 21 publications

The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung

The combined action of mast cell chymase, tryptase and carboxypeptidase A3 protects against melanoma colonization of the lung

Immunohistochemical Analysis of the Mechanistic Target of Rapamycin and Hypoxia Signalling Pathways in Basal Cell Carcinoma and Trichoepithelioma

Are Mast Cells MASTers in Cancer?

Contact Info

Product

Resources

About