Growth of pulmonary metastases of B16 melanoma in mast cell-free mice

Schittek, Anton; Issa, Hussein Abou; Stafford, James H.; Young, Donn C.; Zwilling, Bruce S.; James, Arthur G.

doi:10.1016/0022-4804(85)90006-x

Cited by 20 publications

(15 citation statements)

References 22 publications

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“…[98][99][100] Several studies have shown a tumor cytotoxic role for mast cells in cutaneous malignancies. 14,[101][102][103] Schittek et al demonstrate that mast cell-deficient W/W v mice develop melanoma metastasis more readily than their þ / þ littermates. It has been hypothesized that histamine increases prostacyclin synthesis by endothelial cells, and that prostacyclin has a potent antimetastatic action.…”

Section: 94mentioning

confidence: 99%

“…It has been hypothesized that histamine increases prostacyclin synthesis by endothelial cells, and that prostacyclin has a potent antimetastatic action. 101 Certain mast cell mediators including TNF-a, IL-1, IL-6 and interferon-g have been reported to suppress melanoma cell growth. 102,103 Aoki et al 84 show that mast cells in basal cell carcinoma express mRNA of RANTES, which is a potent chemoattractant for many types of inflammatory cells including neutrophils, eosinophils and monocytes (Figure 7d).…”

Section: 94mentioning

confidence: 99%

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Mast cells and cutaneous malignancies

Ch’ng

Wallis

Yuan³

et al. 2006

Modern Pathology

168

166

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This paper reviews the role of mast cells in the development and progression of basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Mast cells accumulate around cutaneous malignancies. Current evidence suggests that mast cells contribute to the tumorigenesis of cutaneous malignancies through four mechanisms. (1) Immunosuppression: Ultraviolet-B radiation, the most important initiator of cutaneous malignancies, activates mast cells. Upon irradiation of the skin, trans-urocanic acid in the epidermis isomerizes to cis-urocanic acid, which stimulates neuropeptide release from neural c-fibers. These neuropeptides in turn trigger histamine secretion from mast cells, leading to suppression of the cellular immune system. (2) Angiogenesis: Mast cells are the major source of vascular endothelial growth factor in basal cell carcinoma and malignant melanoma. Vascular endothelial growth factor is one of the most potent angiogenic factors, which also induces leakage of other angiogenic factors across the endothelial cell wall into the matrix. Mast cell proteases reorganize the stroma to facilitate endothelial cell migration. As well, heparin, the dominant mast cell proteoglycan, assists in blood-borne metastasis. (3) Degradation of extracellular matrix: Through its own proteases, and indirectly via interaction with other cells, mast cells participate in degradation of the matrix, which is required for tumor spread. (4) Mitogenesis: Mast cell mediators including fibroblast growth factor-2 and interleukin-8 are mitogenic to melanoma cells. Current evidence supports an accessory role for mast cells in the development and progression of cutaneous malignancies. Emerging data, however, also suggest that mast cells might, in fact, have opposing roles in tumor biology, and the microenvironment could polarize mast cells to possess either promoting or inhibitory effects on tumors.

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Section: 94mentioning

confidence: 99%

Section: 94mentioning

confidence: 99%

Mast cells and cutaneous malignancies

Ch’ng

Wallis

Yuan³

et al. 2006

Modern Pathology

168

166

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“…To experimentally address the role of mast cells in malignancies, investigators have assessed various mast cell-deficient mouse models, mainly such in which mast cell-deficiency is a result of defective c-kit signaling [26-31]. However, c-kit is not only expressed in the mast cell niche and, consequently, the c-kit-defective animals can suffer from several additional abnormalities including anemia, alterations in neutrophil populations as well as deficiency of melanocytes, interstitial cells of Cajal and basophils [32].…”

Section: Introductionmentioning

confidence: 99%

Mast cells promote melanoma colonization of lungs

et al. 2016

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Mast cells have been implicated in malignant processes, mainly through clinical correlative studies and by experiments performed using animals lacking mast cells due to defective c-kit signaling. However, mast cell-deficient mouse models based on c-kit defects have recently been questioned for their relevance. Here we addressed the effect of mast cells in a tumor setting by using transgenic Mcpt5-Cre+ R-DTA+ mice, in which the deficiency of mast cells is independent of c-kit defects. Melanoma cells (B16.F10) were administered either subcutaneously or intravenously into Mcpt5-Cre+ R-DTA+ mice or Mcpt5-Cre− R-DTA+ littermate controls, followed by the assessment of formed tumors. In the subcutaneous model, mast cells were abundant in the tumor stroma of control mice but were absent in Mcpt5-Cre+ R-DTA+ mice. However, the absence of mast cells did not affect tumor size. In contrast, after intravenous administration of B16.F10 cells, melanoma colonization of the lungs was markedly reduced in Mcpt5-Cre+ R-DTA+ vs. Mcpt5-Cre− R-DTA+ animals. Decreased melanoma colonization of the lungs in Mcpt5-Cre+ R-DTA+ animals was accompanied by increased inflammatory cell recruitment into the bronchoalveolar lavage fluid, suggesting that mast cells suppress inflammation in this setting. Further, qPCR analysis revealed significant alterations in the expression of Twist and E-cadherin in lungs of Mcpt5-Cre+ R-DTA+ vs. control Mcpt5-Cre− R-DTA+ animals, suggesting an impact of mast cells on epithelial-mesenchymal transition. In conclusion, this study reveals that mast cells promote melanoma colonization of the lung.

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“…Using this approach, some groups have reported an increased susceptibility to tumors in mast cell-deficient mice in certain model systems, [17][18][19] while others reported that mast cell-deficient mice exhibited delayed tumor-associated angiogenesis and/or reduced tumor size and metastasis compared to the corresponding wild-type mice. 10,20,21 One explanation of these apparently discordant findings is that the net contribution of mast cells to different aspects of tumor biology in vivo can be quite variable, and may critically depend on the model system investigated.…”

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confidence: 99%

Decreased susceptibility of mast cell-deficient Kit/Kit mice to the development of 1, 2-dimethylhydrazine-induced intestinal tumors

Wedemeyer

Galli

2005

Laboratory Investigation

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Administration of 1,2-dimethylhydrazine (DMH) induces intestinal epithelial tumors in mice. Increased numbers of mast cells have been reported to occur both within and near a variety of different neoplasms, including DMHinduced intestinal tumors. We investigated the role of the tyrosine kinase receptor, c-kit, and mast cells, in this model by administering DMH to c-kit mutant mast cell-deficient mice and the congenic normal mice. We attempted to induce colonic tumors by administering DMH (20 mg/kg body weight, s.c., weekly for 20 weeks) tomice and W/ W v mice that had been repaired of their mast cell deficiency by adoptive transfer of bone marrow cells derived from the congenic þ / þ mice. The susceptibility to the development of DMH-induced colonic tumors, and the numbers of mast cells associated with these tumors, was evaluated. Normal ( þ / þ ) mice exhibited significantly higher numbers of mast cells in DMH-induced intestinal tumors than in macroscopically normal colonic mucosa. Treatment with DMH induced development of colonic tumors in 97% of þ / þ mice, but in only 32% of the W/W v mice. W/W v mice that had been repaired of their mast cell deficiency by transfer of þ / þ bone marrow cells expressed susceptibility to the development of colonic tumors that was similar to that of wild-type mice. These results show that genetic impairment of c-kit function reduces the susceptibility of mice to DMH-induced colonic tumors, and that defects in bone marrow-derived cells in the W/W v mice contribute significantly to this result. Our findings also are consistent with the possibility that mast cells promote the development of DMHinduced colonic epithelial tumors in mice.

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Growth of pulmonary metastases of B16 melanoma in mast cell-free mice

Cited by 20 publications

References 22 publications

Mast cells and cutaneous malignancies

Mast cells and cutaneous malignancies

Mast cells promote melanoma colonization of lungs

Decreased susceptibility of mast cell-deficient Kit/Kit mice to the development of 1, 2-dimethylhydrazine-induced intestinal tumors

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