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KISSA, K.

Publications and source records attributed to KISSA, K..

3 recordsLinked to original sources

Zebrafish Xenografts Reveal a Context-dependent Roleof PFKFB4 in Melanoma Cell.

Cutaneous melanoma is a highly metastatic cancer in which tumor cell plasticity drives transitions between proliferative and invasive states. The glycolytic regulator PFKFB4 has been implicated in cancer cell motility, but its role in melanoma progression in vivo remains unclear. Using zebrafish larval xenografts, we found that PFKFB4 depletion reduced invasion in MeWo cells without affecting tumor growth, whereas in A375P cells it decreased tumor growth but had no effect on invasion or metastasis. In MeWo, PFKFB4 loss was associated with reduced SNAIL2 expression, while no effect on EMT transcription factors was observed in A375P cells. Rescue experiments indicated that PFKFB4 and SNAIL2 acted independently in regulating Mewo migration in vitro. These findings identify PFKFB4 as a context-dependent regulator of melanoma progression.

cancer biology↗

Melanoma innervation is associated with cancer progression in a zebrafish xenograft model

The peripheral nervous system has a key role in regulating tumour biology in different types of cancer. Here, by modelling aggressive melanoma in larval zebrafish xenografts, we highlight the dynamics of tumour innervation in the tumour microenvironment (TME). Axonogenesis and dendritogenesis are detected in the motoneurons surrounding the melanoma niche and neurogenesis is observed in the nearby population of the enteric nervous system. We also demonstrate the crucial role of catecholamines in promoting melanoma progression, supporting in vivo cancer cell dissemination and invasion. This zebrafish model will allow to uncover neural markers associated with melanoma progression to help in the design of innovative anti-neurogenic therapies targeting specifically the neuronal signals that regulate melanoma progression. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/571512v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1b6d07forg.highwire.dtl.DTLVardef@132770borg.highwire.dtl.DTLVardef@257d05org.highwire.dtl.DTLVardef@132ff72_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LITransplantation of human melanoma cells in 3 dpf zebrafish swim bladder allows the development of aggressive melanoma, which cells invade the surrounding organs and migrate over distant locations. C_LIO_LIThe presence of melanoma cells in the larval zebrafish induces morphological changes in the motoneurons inside the tumour niche, including increased axon length and dendritic arborization. C_LIO_LIThe invasion of melanoma cells in the larval intestine promotes neurogenesis of enteric neurons. C_LIO_LITransplanted melanoma cells display direct contact with enteric neurons in the intestinal region and migrate along axons to escape from the primary cancer mass, as a mechanism similar to vessel co-option during metastatic dissemination. C_LIO_LICatecholamines promote melanoma cell migration and invasion in the zebrafish, modelling melanoma progression. C_LI

cancer biology↗

Macrophage plasticity is Rac signalling and MMP9 dependant

In vitro, depending on extracellular matrix (ECM) architecture, macrophages migrate either in amoeboid or mesenchymal mode; while the first is a general trait of leukocytes, the latter is associated with tissue remodelling via Matrix Metalloproteinases (MMPs). To assess whether these stereotyped migrations could be also observed in a physiological context, we used the zebrafish embryo and monitored macrophage morphology, behaviour and capacity to mobilisation haematopoietic stem/progenitor cells (HSPCs), as a final functional readout. Morphometric analysis identified 4 different cell shapes. Live imaging revealed that macrophages successively adopt all four shapes as they migrate through ECM. Treatment with inhibitors of MMPs or Rac GTPase to abolish mesenchymal migration, suppresses both ECM degradation and HSPC mobilisation while differently affecting macrophage behaviour. This study depicts real time macrophage behaviour in a physiological context and reveals extreme reactivity of these cells constantly adapting and switching migratory shapes to achieve HSPCs proper mobilisation.

cell biology↗