4.5 Article

Identification of differentially expressed genes in spontaneously regressing melanoma using the MeLiM Swine Model

期刊

PIGMENT CELL & MELANOMA RESEARCH
卷 21, 期 2, 页码 147-161

出版社

BLACKWELL PUBLISHING
DOI: 10.1111/j.1755-148X.2008.00442.x

关键词

swine melanoma; suppression subtractive hybridization; differential gene expression; real-time PCR; tumour regression

向作者/读者索取更多资源

Partial and some few cases of complete spontaneous regression have been observed in cutaneous melanoma patients but little is known about the molecular mechanisms involved. The Melanoblastoma-bearing Libechov Minipig (MeLiM) is a suitable animal model to study the phenomenon of spontaneous regression because MeLiM pigs exhibit naturally occurring melanomas which regress completely 6 months after birth. In this study, we used suppression subtractive hybridization (SSH) to identify molecular determinants of melanoma regression within swine melanoma tissues and melanoma cell cultures. Several markers involved in cell-adhesion, -communication, -motility, signal transduction, negative regulation of cell proliferation, transport and immune response were identified that correlated with melanoma regression whereas the main genes involved in melanin synthesis showed a strong downregulation. For the most differentially expressed genes, we validated the results obtained by SSH with qRT-PCR and with immunohistochemistry for some of them (CD9, MITF, RARRES1). Most notable, for the first time in melanoma, we identified the retinoic acid responder 1 gene (RARRES1) as a main actor of the regression process in melanoma. This first gene expression study in swine melanoma regression, may contribute to the finding of new therapeutic targets for human melanoma treatment.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Medicine, Research & Experimental

CRISPR screens identify tumor-promoting genes conferring melanoma cell plasticity and resistance

Arthur Gautron, Laura Bachelot, Marc Aubry, Delphine Leclerc, Anais M. Quemener, Sebastien Corre, Florian Rambow, Anais Paris, Nina Tardif, Heloise M. Leclair, Oskar Marin-Bejar, Cedric Coulouarn, Jean-Christophe Marine, Marie-Dominique Galibert, David Gilot

Summary: Genetic drivers of melanoma development and therapy resistance have been identified, but non-genetic mechanisms are less understood. Through in vivo CRISPR screens, SMAD3, BIRC3, and SLC9A5 were found to play key roles in BRAFi resistance. Upregulation of SMAD3 was linked to resistance prediction and chemical inhibition of SMAD3 showed promise in targeting persister cells associated with melanoma.

EMBO MOLECULAR MEDICINE (2021)

Review Biochemistry & Molecular Biology

Epithelial-to-mesenchymal-like transition events in melanoma

Dennis Pedri, Panagiotis Karras, Ewout Landeloos, Jean-Christophe Marine, Florian Rambow

Summary: The review discusses the emergence of a process similar to EMT in melanoma, as well as how comparative analysis with EMT state(s) in epithelial cancers can provide clues for identifying clinically relevant biomarkers for prognosis and new therapeutic strategies.

FEBS JOURNAL (2022)

Article Biology

A role for Dynlt3 in melanosome movement, distribution, acidity and transfer

Zackie Aktary, Alejandro Conde-Perez, Florian Rambow, Mathilde Di Marco, Francois Amblard, Ilse Hurbain, Graca Raposo, Cedric Delevoye, Sylvie Coscoy, Lionel Larue

Summary: Dynlt3 plays a crucial role in melanosome transport, maturation, and transfer to keratinocytes, essential for proper skin pigmentation. The Wnt/beta catenin signaling pathway regulates Dynlt3 levels, contributing to the control of melanocyte transport and skin pigmentation.

COMMUNICATIONS BIOLOGY (2021)

Article Oncology

Evolutionary predictability of genetic versus nongenetic resistance to anticancer drugs in melanoma

Oskar Marin-Bejar, Aljosja Rogiers, Michael Dewaele, Julia Femel, Panagiotis Karras, Joanna Pozniak, Greet Bervoets, Nina Van Raemdonck, Dennis Pedri, Toon Swings, Jonas Demeulemeester, Sara Vander Borght, Stefan Lehnert, Francesca Bosisio, Joost J. van den Oord, Isabelle Vanden Bempt, Diether Lambrechts, Thierry Voet, Oliver Bechter, Helen Rizos, Mitchell P. Levesque, Eleonora Leucci, Amanda W. Lund, Florian Rambow, Jean-Christophe Marine

Summary: Therapy resistance in melanoma can arise from genetic or nongenetic mechanisms, with the emergence of neural crest stem cells in minimal residual disease playing a role in the development of nongenetic resistance. Ablation of these cells through focal adhesion kinase inhibition delays tumor relapse and reveals that ultimately resistant tumors exhibit genetic alterations that increase sensitivity to specific inhibitors.

CANCER CELL (2021)

Article Cell Biology

A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression

Ioannis I. Verginadis, Harris Avgousti, James Monslow, Giorgos Skoufos, Frank Chinga, Kyle Kim, Nektaria Maria Leli, Ilias V. Karagounis, Brett I. Bell, Anastasia Velalopoulou, Carlo Salas Salinas, Victoria S. Wu, Yang Li, Jiangbin Ye, David A. Scott, Andrei L. Osterman, Arjun Sengupta, Aalim Weljie, Menggui Huang, Duo Zhang, Yi Fan, Enrico Radaelli, John W. Tobias, Florian Rambow, Panagiotis Karras, Jean-Christophe Marine, Xiaowei Xu, Artemis G. Hatzigeorgiou, Sandra Ryeom, J. Alan Diehl, Serge Y. Fuchs, Ellen Pure, Constantinos Koumenis

Summary: Bidirectional signalling between the tumour and stroma plays a crucial role in shaping tumour aggressiveness and metastasis. ATF4, a major effector of the Integrated Stress Response, regulates collagen biosynthesis and deposition in perivascular cancer-associated fibroblasts (CAFs), thereby supporting angiogenesis and progression in melanoma and pancreatic cancer.

NATURE CELL BIOLOGY (2022)

Article Multidisciplinary Sciences

A cellular hierarchy in melanoma uncouples growth and metastasis

Panagiotis Karras, Ignacio Bordeu, Joanna Pozniak, Ada Nowosad, Cecilia Pazzi, Nina Van Raemdonck, Ewout Landeloos, Yannick Van Herck, Dennis Pedri, Greet Bervoets, Samira Makhzami, Jia Hui Khoo, Benjamin Pavie, Jochen Lamote, Oskar Marin-Bejar, Michael Dewaele, Han Liang, Xingju Zhang, Yichao Hua, Jasper Wouters, Robin Browaeys, Gabriele Bergers, Yvan Saeys, Francesca Bosisio, Joost van den Oord, Diether Lambrechts, Anil K. Rustgi, Oliver Bechter, Cedric Blanpain, Benjamin D. Simons, Florian Rambow, Jean-Christophe Marine

Summary: By combining mouse genetics, single-cell and spatial transcriptomics, lineage tracing and quantitative modelling, the researchers provide evidence of a hierarchical model of tumour growth in melanoma and reveal the spatial and temporal diversity and trajectories of melanoma cell states. They show that tumorigenic competence is associated with a spatially localized perivascular niche and that only a fraction of cells are fated to fuel primary tumour growth, while another fraction constitutes a pool of metastatic initiating cells that switch cell identity during dissemination to secondary organs. These findings highlight the importance of targeting microenvironmental cues to interfere with the cancer cell reprogramming activity.

NATURE (2022)

Correction Multidisciplinary Sciences

A cellular hierarchy in melanoma uncouples growth and metastasis (vol 610, pg 190, 2022)

Panagiotis Karras, Ignacio Bordeu, Joanna Pozniak, Ada Nowosad, Cecilia Pazzi, Nina Van Raemdonck, Ewout Landeloos, Yannick Van Herck, Dennis Pedri, Greet Bervoets, Samira Makhzami, Jia Hui Khoo, Benjamin Pavie, Jochen Lamote, Oskar Marin-Bejar, Michael Dewaele, Han Liang, Xingju Zhang, Yichao Hua, Jasper Wouters, Robin Browaeys, Gabriele Bergers, Yvan Saeys, Francesca Bosisio, Joost van den Oord, Diether Lambrechts, Anil K. Rustgi, Oliver Bechter, Cedric Blanpain, Benjamin D. Simons, Florian Rambow, Jean-Christophe Marine

NATURE (2022)

Correction Oncology

Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1+ T lymphocyte niches through a feed-forward loop (vol 40, pg 1600, 2022)

Yichao Hua, Gerlanda Vella, Florian Rambow, Elizabeth Allen, Asier Antoranz Martinez, Marie Duhamel, Akira Takeda, Sirpa Jalkanen, Steffie Junius, Ann Smeets, David Nittner, Stefanie Dimmeler, Thomas Hehlgans, Adrian Liston, Francesca Maria Bosisio, Giuseppe Floris, Damya Laoui, Maija Hollmen, Diether Lambrechts, Pascal Merchiers, Jean-Christophe Marine, Susan Schlenner, Gabriele Bergers

CANCER CELL (2023)

Article Oncology

Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1+ T lymphocyte niches through a feed-forward loop

Yichao Hua, Gerlanda Vella, Florian Rambow, Elizabeth Allen, Asier Antoranz Martinez, Marie Duhamel, Akira Takeda, Sirpa Jalkanen, Steffie Junius, Ann Smeets, David Nittner, Stefanie Dimmeler, Thomas Hehlgans, Adrian Liston, Francesca Maria Bosisio, Giuseppe Floris, Damya Laoui, Maija Hollmen, Diether Lambrechts, Pascal Merchiers, Jean-Christophe Marine, Susan Schlenner, Gabriele Bergers

Summary: The lack of T cell infiltrates hinders effective immunotherapy in cancer, while the formation of tumor-associated tertiary-lymphoid-like structures (TA-TLLSs) is associated with a good prognosis. This study reveals that antiangiogenic immune-modulating therapies can induce the transformation of postcapillary venules into inflamed high-endothelial venules (HEVs) through lymphotoxin/lymphotoxin beta receptor (LT/LTbR) signaling. Tumor HEVs enhance intratumoral lymphocyte influx and promote the differentiation of CD8 T cell progenitors into effector cells, contributing to tumor immunotherapy.

CANCER CELL (2022)

Article Biochemistry & Molecular Biology

The mechanosensitive TRPV2 calcium channel promotes human melanoma invasiveness and metastatic potential

Kenji F. Shoji, Elsa Bayet, Sabrina Leverrier-Penna, Dahiana Le Devedec, Aude Mallavialle, Severine Marionneau-Lambot, Florian Rambow, Raul Perret, Aurelie Joussaume, Roselyne Viel, Alain Fautrel, Amir Khammari, Bruno Constantin, Sophie Tartare-Deckert, Aubin Penna

Summary: Melanoma, a highly aggressive cancer, is driven by aberrant cell motility behaviors and the ability to rapidly metastasize. This study reveals the prominent expression of the plasma membrane TRPV2 calcium channel in melanoma tumors, directly linked to metastatic dissemination. TRPV2 activity confers migratory and invasive potentials in both in vitro and in vivo settings, while silencing TRPV2 in highly metastatic melanoma cells prevents aggressive behavior. The TRPV2 channel, localized at the leading edge of invasive melanoma cells, regulates calcium-mediated activation of calpain and subsequent cleavage of talin, along with F-actin organization. Overexpression of TRPV2 in human melanoma tissues is associated with advanced malignancy and poor prognosis, suggesting its potential as a biomarker. By controlling adhesion and motility, the mechanosensitive TRPV2 channel offers a new therapeutic option for migrastatics in metastatic melanoma treatment.

EMBO REPORTS (2023)

Article Oncology

Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

Ali Talebi, Vincent de Laat, Xander Spotbeen, Jonas Dehairs, Florian Rambow, Aljosja Rogiers, Frank Vanderhoydonc, Lara Rizotto, Melanie Planque, Ginevra Doglioni, Sahar Motamedi, David Nittner, Tania Roskams, Patrizia Agostinis, Oliver Bechter, Veerle Boecxstaens, Marjan Garmyn, Marie O'Farrell, Alan Wagman, George Kemble, Eleonora Leucci, Sarah-Maria Fendt, Jean-Christophe Marine, Johannes V. V. Swinnen

Summary: This study identifies the role of FASN in therapy resistance in cancer. By inhibiting FASN and inducing ROS, therapy resistance can be delayed. The combination of MAPK inhibitors, FASN inhibitors, and ROS inducers significantly increases survival in therapy-resistant models.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2023)

Article Multidisciplinary Sciences

CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours

Bastian Kruse, Anthony C. Buzzai, Naveen Shridhar, Andreas D. Braun, Susan Gellert, Kristin Knauth, Joanna Pozniak, Johannes Peters, Paulina Dittmann, Miriam Mengoni, Tetje Cornelia van der Sluis, Simon Hoehn, Asier Antoranz, Anna Krone, Yan Fu, Di Yu, Magnus Essand, Robert Geffers, Dimitrios Mougiakakos, Sascha Kahlfuss, Hamid Kashkar, Evelyn Gaffal, Francesca M. Bosisio, Oliver Bechter, Florian Rambow, Jean-Christophe Marine, Wolfgang Kastenmueller, Andreas J. Mueller, Thomas Tueting

Summary: Most clinically applied cancer immunotherapies rely on direct recognition and killing of tumor cells by CD8(+) cytolytic T cells. However, the effectiveness of these strategies is limited by the emergence of MHC-deficient tumor cells and immunosuppressive tumor microenvironment. In this study, researchers have discovered that a small number of CD4(+) T cells can eliminate MHC-deficient tumors that escape CD8(+) T cell targeting. CD4(+) effector T cells cluster at tumor invasive margins and interact with MHC-II(+)CD11c(+) antigen-presenting cells, leading to the activation of tumoricidal myeloid cells. Together, CD4(+) T cells and tumoricidal myeloid cells induce inflammatory cell death and eradicate interferon-unresponsive and MHC-deficient tumors, suggesting a potential strategy to complement current cancer immunotherapies.

NATURE (2023)

Article Oncology

Glucocorticoid activation by HSD11B1 limits T cell-driven interferon signaling and response to PD-1 blockade in melanoma

Luiza Martins Nascentes Melo, Dayana Herrera-Rios, Daniel Hinze, Stefanie Loeffek, Irem Oezel, Roberta Turiello, Juliane Klein, Sonia Leonardelli, Isa-Vanessa Westedt, Yahya Al-Matary, Sara Egea-Rodriguez, Alexandra Brenzel, Maja Bau, Antje Sucker, Eva Hadaschik, Florian Wirsdoerfer, Helmut Hanenberg, Niklas Uhlenbrock, Daniel Rauh, Joanna Pozniak, Florian Rambow, Jean-Christophe Marine, Maike Effern, Nicole Glodde, Dirk Schadendorf, Jadwiga Jablonska, Michael Hoelzel, Iris Helfrich

Summary: This study identified HSD11B1 as a negative feedback mechanism that limits the efficacy of PD-1 blockade, and showed that HSD11B1 inhibitors can enhance the effectiveness of immunotherapy for melanoma. Additionally, high levels of HSD11B1 were associated with poor responses to immune checkpoint inhibitors in patients with advanced melanoma.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

Article Biotechnology & Applied Microbiology

Enhanced chromatin accessibility contributes to X chromosome dosage compensation in mammals

Irene Talon, Adrian Janiszewski, Bart Theeuwes, Thomas Lefevre, Juan Song, Greet Bervoets, Lotte Vanheer, Natalie De Geest, Suresh Poovathingal, Ryan Allsop, Jean-Christophe Marine, Florian Rambow, Thierry Voet, Vincent Pasque

Summary: Our study reveals that intrinsic compensatory mechanisms exist in mammalian cells, involving modulation of chromatin accessibility to counteract imbalances in gene dosage between the X chromosome and autosomes caused by evolutionary changes or X chromosome inactivation in vitro. Through genome-wide approaches, allele-specific ATAC-seq, and single-cell RNA-seq, we demonstrate increased chromatin accessibility on the upregulated active X chromosome compared to autosomes in female embryonic fibroblasts and during reprogramming to pluripotency. Additionally, our data show that ZFP42/REX1, a gene associated with pluripotency that evolved specifically in placental mammals, targets multiple X-linked genes, suggesting an evolutionary link between ZFP42/REX1, X chromosome reactivation, and pluripotency.

GENOME BIOLOGY (2021)

Article Oncology

Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia

Claudie Bosc, Estelle Saland, Aurelie Bousard, Noemie Gadaud, Marie Sabatier, Guillaume Cognet, Thomas Farge, Emeline Boet, Mathilde Gotanegre, Nesrine Aroua, Pierre-Luc Mouchel, Nathaniel Polley, Clement Larrue, Eleonore Kaphan, Muriel Picard, Ambrine Sahal, Latifa Jarrou, Marie Tosolini, Florian Rambow, Florence Cabon, Nathalie Nicot, Laura Poillet-Perez, Yujue Wang, Xiaoyang Su, Quentin Fovez, Jerome Kluza, Rafael Jose Arguello, Celine Mazzotti, Herve Avet-Loiseau, Francois Vergez, Jerome Tamburini, Jean-Jacques Fournie, Ing S. Tiong, Andrew H. Wei, Tony Kaoma, Jean-Christophe Marine, Christian Recher, Lucille Stuani, Carine Joffre, Jean-Emmanuel Sarry

Summary: Therapy resistance in AML is linked to high mitochondrial oxidative phosphorylation identified by MitoScore. Targeting mitochondrial metabolism can delay AML relapse, highlighting the central role of mitochondrial adaptation in AML therapy.

NATURE CANCER (2021)

暂无数据