scholarly journals NAADP-Dependent Ca2+ Signaling Controls Melanoma Progression, Metastatic Dissemination and Neoangiogenesis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Annarita Favia ◽  
Irene Pafumi ◽  
Marianna Desideri ◽  
Fabrizio Padula ◽  
Camilla Montesano ◽  
...  
Keyword(s):  
Metastatic Dissemination ◽  
Melanoma Progression

scholarly journals New Insights into the Role of Sphingolipid Metabolism in Melanoma

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1967 ◽  
Author(s):  
Lorry Carrié ◽  
Mathieu Virazels ◽  
Carine Dufau ◽  
Anne Montfort ◽  
Thierry Levade ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Skin Cancer ◽  
Immune Responses ◽  
Cutaneous Melanoma ◽  
Sphingolipid Metabolism ◽  
Metastatic Dissemination ◽  
Resistance To Treatment ◽  
Melanoma Progression ◽  
The Impact

Cutaneous melanoma is a deadly skin cancer whose aggressiveness is directly linked to its metastatic potency. Despite remarkable breakthroughs in term of treatments with the emergence of targeted therapy and immunotherapy, the prognosis for metastatic patients remains uncertain mainly because of resistances. Better understanding the mechanisms responsible for melanoma progression is therefore essential to uncover new therapeutic targets. Interestingly, the sphingolipid metabolism is dysregulated in melanoma and is associated with melanoma progression and resistance to treatment. This review summarises the impact of the sphingolipid metabolism on melanoma from the initiation to metastatic dissemination with emphasis on melanoma plasticity, immune responses and resistance to treatments.

scholarly journals Tumor cell intrinsic TLR4 signaling promotes melanoma progression and metastatic dissemination

2021 ◽  
Author(s):  
Meri Rogava ◽  
Andreas Dominik Braun ◽  
Tetje Cornelia Sluis ◽  
Naveen Shridhar ◽  
Thomas Tüting ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tlr4 Signaling ◽  
Metastatic Dissemination ◽  
Melanoma Progression

Role of MMPs in Metastatic Dissemination: Implications for Therapeutic Advances

2011 ◽  
Vol 12 (11) ◽  
pp. 1937-1947 ◽  
Author(s):  
D. Raffo ◽  
O. Pontiggia ◽  
M. Simian
Keyword(s):  
Metastatic Dissemination

CD147 Promotes Melanoma Progression Through Hypoxia-Induced MMP2 Activation

2013 ◽  
Vol 11 (666) ◽  
pp. 1-2 ◽  
Author(s):  
W. Zeng ◽  
J. Su ◽  
L. Wu ◽  
D. Yang ◽  
T. Long ◽  
...  
Keyword(s):  
Melanoma Progression

scholarly journals Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gautier Follain ◽  
Naël Osmani ◽  
Valentin Gensbittel ◽  
Nandini Asokan ◽  
Annabel Larnicol ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Metastatic Progression ◽  
Metastatic Dissemination ◽  
Secondary Tumors ◽  
Flow Profiles ◽  
Endothelial Response ◽  
Life Threatening

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

scholarly journals Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 726
Author(s):  
Christopher Groth ◽  
Ludovica Arpinati ◽  
Merav E. Shaul ◽  
Nina Winkler ◽  
Klara Diester ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
Receptor Expression ◽  
Myeloid Derived Suppressor Cells ◽  
Melanoma Progression ◽  
Relative Contribution ◽  
Immunosuppressive Tumor Microenvironment ◽  
Metastatic Sites

Background: Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, the disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented by myeloid-derived suppressor cells (MDSC). However, the relative contribution of the polymorphonuclear (PMN) and monocytic (M) MDSC subsets to melanoma progression is not clear. Here, we compared both subsets regarding their immunosuppressive capacity and recruitment mechanisms. Furthermore, we inhibited PMN-MDSC migration in vivo to determine its effect on tumor progression. Methods: Using the RET transgenic melanoma mouse model, we investigated the immunosuppressive function of MDSC subsets and chemokine receptor expression on these cells. The effect of CXCR2 inhibition on PMN-MDSC migration and tumor progression was studied in RET transgenic mice and in C57BL/6 mice after surgical resection of primary melanomas. Results: Immunosuppressive capacity of intratumoral M- and PMN-MDSC was comparable in melanoma bearing mice. Anti-CXCR2 therapy prolonged survival of these mice and decreased the occurrence of distant metastasis. Furthermore, this therapy reduced the infiltration of melanoma lesions and pre-metastatic sites with PMN-MDSC that was associated with the accumulation of natural killer (NK) cells. Conclusions: We provide evidence for the tumor−promoting properties of PMN-MDSC as well as for the anti-tumor effects upon their targeting in melanoma bearing mice.

scholarly journals The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Positive Association ◽  
Tumor Stage ◽  
Melanoma Cells ◽  
Melanoma Progression

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

scholarly journals INDUCTION OF METASTASIS OF FROG CARCINOMA BY INCREASE OF ENVIRONMENTAL TEMPERATURE

1949 ◽  
Vol 89 (3) ◽  
pp. 269-278 ◽  
Author(s):  
Balduin Lucké ◽  
Hans Schlumberger
Keyword(s):  
Tissue Culture ◽  
Elevated Temperature ◽  
Constant Temperature ◽  
Rana Pipiens ◽  
Environmental Temperature ◽  
Kidney Tumors ◽  
Primary Tumors ◽  
Metastatic Dissemination ◽  
Leopard Frogs ◽  
Tumor Bearing

Metastasis of the kidney carcinoma of leopard frogs (Rana pipiens) has been induced by exposing tumor-bearing animals for approximately 50 days to a constant temperature of 28°C. Under these conditions 54 per cent of the frogs developed secondary growths, whereas in groups kept at 18° or at 7° metastatic dissemination was found in only 6 per cent. Moreover, at the elevated temperature the metastases were usually more numerous and more widely disseminated; they were also fairly uniform in size, suggesting that they had developed at nearly the same time. Dissemination of the kidney tumors was influenced by the nutritional state of the frogs, occurring more readily in well nourished than in poorly nourished animals. Periodic Roentgen ray examinations showed that the size of the primary tumors was not significantly or uniformly affected during the course of the experiments. No correlation was found between change in size of the kidney tumors and the incidence of their metastasis. Although the mechanism by which temperature induces metastasis of frog carcinoma cannot as yet be elucidated, previous experiments with this tumor indicate that certain factors at least may be involved: Elevation of temperature has been found to cause more ready detachment of cells of frog carcinoma in tissue culture; to bring about increased velocity of locomotion of the detached cells; to lead more promptly and efficiently to vascularization of transplants; and to effect their greater invasiveness.

scholarly journals 588 Essential role of periostin in inflammation-associated melanoma progression in human and mouse

2017 ◽  
Vol 137 (10) ◽  
pp. S293
Author(s):  
F. Ohno ◽  
T. Nakahara ◽  
M. Nakahara ◽  
S. Nunomura ◽  
K. Izuhara ◽  
...  
Keyword(s):  
Essential Role ◽  
Melanoma Progression ◽  
Human And Mouse
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