Mast cells protect from skin tumor development and limit tumor growth during cutaneousde novocarcinogenesis in a Kit-dependent mouse model

Accumulating evidence has highlighted the accumulation of mast cells (MCs) in tumors. However, their impact on tumor development remained controversial. Indeed, cumulative data indicate an enigmatic role for MCs in cancer, whereby depending on the circumstances, which still need to be resolved, MCs function to promote or restrict tumor growth. By responding to multiple stimuli MCs release multiple inflammatory mediators, that contribute to the resolution of infection and resistance to envenomation, but also have the potency to promote or inhibit malignancy. Thus, MCs seem to possess the power to define tumor projections. Given this remarkable plasticity of MC responsiveness, there is an urgent need of understanding how MCs are activated in the tumor microenvironment (TME). We have recently reported on the direct activation of MCs upon contact with cancer cells by a mechanism involving an autocrine formation of adenosine and signaling by the A3 adenosine receptor. Here we summarized the evidence on the role of adenosine signaling in cancer, in MC mediated inflammation and in the MC-cancer crosstalk.

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In Vivo Fluorescence Imaging and Urinary Monoamines as Surrogate Biomarkers of Disease Progression in a Mouse Model of Pheochromocytoma

Endocrinology ◽

10.1210/en.2014-1431 ◽

2014 ◽

Vol 155 (11) ◽

pp. 4149-4156 ◽

Cited By ~ 8

Author(s):

Martin Ullrich ◽

Ralf Bergmann ◽

Mirko Peitzsch ◽

Marc Cartellieri ◽

Nan Qin ◽

...

Keyword(s):

Mouse Model ◽

Tumor Growth ◽

Tumor Progression ◽

Fluorescence Imaging ◽

Fluorescence Intensity ◽

Tumor Development ◽

Treatment Strategies ◽

Small Animal ◽

Whole Body

Abstract Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumor arising from catecholamine-producing chromaffin cells. Especially for metastatic PHEO, the availability of animal models is essential for developing novel therapies. For evaluating therapeutic outcome in rodent PHEO models, reliable quantification of multiple organ lesions depends on dedicated small-animal in vivo imaging, which is still challenging and only available at specialized research facilities. Here, we investigated whether whole-body fluorescence imaging and monitoring of urinary free monoamines provide suitable parameters for measuring tumor progression in a murine allograft model of PHEO. We generated an mCherry-expressing mouse PHEO cell line by lentiviral gene transfer. These cells were injected subcutaneously into nude mice to perform whole-body fluorescence imaging of tumor development. Urinary free monoamines were measured by liquid chromatography with tandem mass spectrometry. Tumor fluorescence intensity and urinary outputs of monoamines showed tumor growth–dependent increases (P < .001) over the 30 days of monitoring post-tumor engraftment. Concomitantly, systolic blood pressure was increased significantly during tumor growth. Tumor volume correlated significantly (P < .001) and strongly with tumor fluorescence intensity (rs = 0.946), and urinary outputs of dopamine (rs = 0.952), methoxytyramine (rs = 0.947), norepinephrine (rs = 0.756), and normetanephrine (rs = 0.949). Dopamine and methoxytyramine outputs allowed for detection of lesions at diameters below 2.3 mm. Our results demonstrate that mouse pheochromocytoma (MPC)-mCherry cell tumors are functionally similar to human PHEO. Both tumor fluorescence intensity and urinary outputs of free monoamines provide precise parameters of tumor progression in this sc mouse model of PHEO. This animal model will allow for testing new treatment strategies for chromaffin cell tumors.

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Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms222413377 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13377

Author(s):

Nada Ragab ◽

Julia Bauer ◽

Dominik S. Botermann ◽

Anja Uhmann ◽

Heidi Hahn

Keyword(s):

Mouse Model ◽

Tumor Growth ◽

Time Window ◽

Tumor Development ◽

Tumor Stage ◽

Time Frame ◽

Embryonal Rhabdomyosarcoma ◽

Tumor Differentiation ◽

Specific Time ◽

Free Survival

In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisible ERMS precursor stage at 4 weeks of age, tumor development was enforced upon oncHRAS and oncKRAS but not by oncNRAS, which instead initiated tumor differentiation. These data indicate that oncRAS-associated processes differ from each other in dependency on the isoform and their occurrence during tumor development. Here, we investigated the outcome of oncNRAS induction at an earlier ERMS precursor stage at 2 weeks of age. In this setting, oncNRAS accelerates tumor growth because it significantly shortens the ERMS-free survival and increases the ERMS incidence. However, it does not seem to alter the differentiation of the tumors. It is also not involved in tumor initiation. Together, these data show that oncNRAS mutations can accelerate tumor growth when targeting immature ERMS precursors within a specific time window, in which the precursors are permissive to the mutation and show that oncNRAS-associated processes differ from each other in dependency on their occurrence during tumor development.

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