New Insights into the Exosome-Induced Migration of Uveal Melanoma Cells and the Pre-Metastatic Niche Formation in the Liver
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Cell Culture Conditions
2.2. Viral Production and Cell Infections
2.3. Extracellular Vesicles (EVs) Isolation
2.4. Cryo-Electron Microscopy of EVs
2.5. EVs Labeling and Cell Uptake Assay
2.6. Co-Culture Assay
2.7. Cell Adhesion Assay
2.8. Migration Assays
2.9. Proteomic Analysis
2.9.1. Protein Extraction and Digestion of EVs
2.9.2. LC-MS/MS Analysis of EVs
2.9.3. Western Blot Analysis
2.9.4. Immunofluorescence Analysis
2.9.5. Rac1 and RhoA Activity Assay
2.10. Total RNA Isolation, Reverse Transcription, and Quantitative RT-qPCR Analysis
2.11. Data Analysis and Biological Functional Network of the EV Protein Cargo
2.12. Statistical Analysis
3. Results
3.1. Isolation and Characterization of UM Exosomes
3.2. Differential Proteomic Profiles of Exosomes Derived from UM Metastatic Cells
3.3. Proteomic Profile and Network of Functional Molecular Interactions of EV Protein Cargo Identify Cell Movement Modes
3.4. Proteomic Analysis of UM-Derived EVs Reveals a Distinct Integrin Profile in Metastatic and Non-Metastatic Cells
3.5. Exosome Uptake by Hepatic Stellate Cells In Vitro
3.6. UM-Derived Exosomes Induce a Pro-Fibrotic and Inflammatory Phenotype in HHSC
3.7. UM Exosome-Treated LX2/THP-1 Simulates Cell Adhesion and Migration of UM Cells
4. Discussion
4.1. Proteomic Analysis of EVs Secreted by UM-Cells Reveals Key Proteins Related to Migration and Invasion
4.2. Contribution of EVs Secreted by UM Cells to Pre-Metastatic Niche Formation and Liver Colonization
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Kaliki, S.; Shields, C.L. Uveal melanoma: Relatively rare but deadly cancer. Eye 2017, 31, 241–257. [Google Scholar] [CrossRef]
- Kastelan, S.; Mrazovac Zimak, D.; Ivankovic, M.; Markovic, I.; Gverovic Antunica, A. Liver metastasis in uveal melanoma—Treatment options and clinical outcome. Front. Biosci. (Landmark Ed.) 2022, 27, 72. [Google Scholar] [CrossRef] [PubMed]
- Landreville, S.; Agapova, O.A.; Harbour, J.W. Emerging insights into the molecular pathogenesis of uveal melanoma. Future Oncol. 2008, 4, 629–636. [Google Scholar] [CrossRef]
- Hassel, J.C.; Piperno-Neumann, S.; Rutkowski, P.; Baurain, J.F.; Schlaak, M.; Butler, M.O.; Sullivan, R.J.; Dummer, R.; Kirkwood, J.M.; Orloff, M.; et al. Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. N. Engl. J. Med. 2023, 389, 2256–2266. [Google Scholar] [CrossRef]
- Robertson, A.G.; Shih, J.; Yau, C.; Gibb, E.A.; Oba, J.; Mungall, K.L.; Hess, J.M.; Uzunangelov, V.; Walter, V.; Danilova, L.; et al. Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. Cancer Cell 2017, 32, 204–220.e215. [Google Scholar] [CrossRef] [PubMed]
- Bustamante, P.; Piquet, L.; Landreville, S.; Burnier, J.V. Uveal melanoma pathobiology: Metastasis to the liver. Semin. Cancer Biol. 2021, 71, 65–85. [Google Scholar] [CrossRef] [PubMed]
- Brodt, P. Role of the Microenvironment in Liver Metastasis: From Pre- to Prometastatic Niches. Clin. Cancer Res. 2016, 22, 5971–5982. [Google Scholar] [CrossRef] [PubMed]
- Lobb, R.J.; Lima, L.G.; Moller, A. Exosomes: Key mediators of metastasis and pre-metastatic niche formation. Semin. Cell Dev. Biol. 2017, 67, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Sceneay, J.; Smyth, M.J.; Moller, A. The pre-metastatic niche: Finding common ground. Cancer Metastasis Rev. 2013, 32, 449–464. [Google Scholar] [CrossRef]
- Pegtel, D.M.; Gould, S.J. Exosomes. Annu. Rev. Biochem. 2019, 88, 487–514. [Google Scholar] [CrossRef]
- Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science 2020, 367, eaau6977. [Google Scholar] [CrossRef] [PubMed]
- Wortzel, I.; Dror, S.; Kenific, C.M.; Lyden, D. Exosome-Mediated Metastasis: Communication from a Distance. Dev. Cell 2019, 49, 347–360. [Google Scholar] [CrossRef] [PubMed]
- Angi, M.; Kalirai, H.; Prendergast, S.; Simpson, D.; Hammond, D.E.; Madigan, M.C.; Beynon, R.J.; Coupland, S.E. In-depth proteomic profiling of the uveal melanoma secretome. Oncotarget 2016, 7, 49623–49635. [Google Scholar] [CrossRef]
- Pardo, M.; Garcia, A.; Antrobus, R.; Blanco, M.J.; Dwek, R.A.; Zitzmann, N. Biomarker discovery from uveal melanoma secretomes. identification of gp100 and cathepsin D in patient serum. J. Proteome Res. 2007, 6, 2802–2811. [Google Scholar] [CrossRef]
- Seitz, T.; John, N.; Sommer, J.; Dietrich, P.; Thasler, W.E.; Hartmann, A.; Evert, K.; Lang, S.A.; Bosserhoff, A.; Hellerbrand, C. Role of Fibroblast Growth Factors in the Crosstalk of Hepatic Stellate Cells and Uveal Melanoma Cells in the Liver Metastatic Niche. Int. J. Mol. Sci. 2022, 23, 11524. [Google Scholar] [CrossRef] [PubMed]
- Ambrosini, G.; Rai, A.J.; Carvajal, R.D.; Schwartz, G.K. Uveal Melanoma Exosomes Induce a Prometastatic Microenvironment through Macrophage Migration Inhibitory Factor. Mol. Cancer Res. 2022, 20, 661–669. [Google Scholar] [CrossRef] [PubMed]
- Piquet, L.; Dewit, L.; Schoonjans, N.; Millet, M.; Berube, J.; Gerges, P.R.A.; Bordeleau, F.; Landreville, S. Synergic Interactions between Hepatic Stellate Cells and Uveal Melanoma in Metastatic Growth. Cancers 2019, 11, 1043. [Google Scholar] [CrossRef]
- Surman, M.; Hoja-Lukowicz, D.; Szwed, S.; Kedracka-Krok, S.; Jankowska, U.; Kurtyka, M.; Drozdz, A.; Litynska, A.; Stepien, E.; Przybylo, M. An Insight into the Proteome of Uveal Melanoma-Derived Ectosomes Reveals the Presence of Potentially Useful Biomarkers. Int. J. Mol. Sci. 2019, 20, 3789. [Google Scholar] [CrossRef]
- Tsering, T.; Laskaris, A.; Abdouh, M.; Bustamante, P.; Parent, S.; Jin, E.; Ferrier, S.T.; Arena, G.; Burnier, J.V. Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation. Cancers 2020, 12, 2923. [Google Scholar] [CrossRef]
- Ramos, R.; Cabre, E.; Vinyals, A.; Lorenzo, D.; Ferreres, J.R.; Varela, M.; Goma, M.; Paules, M.J.; Gutierrez, C.; Piulats, J.M.; et al. Orthotopic murine xenograft model of uveal melanoma with spontaneous liver metastasis. Melanoma Res. 2023, 33, 1–11. [Google Scholar] [CrossRef]
- Li, K.; Chen, Y.; Li, A.; Tan, C.; Liu, X. Exosomes play roles in sequential processes of tumor metastasis. Int. J. Cancer 2019, 144, 1486–1495. [Google Scholar] [CrossRef] [PubMed]
- Han, W.; Duan, Z. Roles of exosomes in liver metastases: Novel diagnosis and treatment choices. J. Cell Physiol. 2019, 234, 21588–21600. [Google Scholar] [CrossRef]
- Costa-Silva, B.; Aiello, N.M.; Ocean, A.J.; Singh, S.; Zhang, H.; Thakur, B.K.; Becker, A.; Hoshino, A.; Mark, M.T.; Molina, H.; et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 2015, 17, 816–826. [Google Scholar] [CrossRef] [PubMed]
- Palazzolo, G.; Albanese, N.N.; Di Cara, G.; Gygax, D.; Vittorelli, M.L.; Pucci-Minafra, I. Proteomic analysis of exosome-like vesicles derived from breast cancer cells. Anticancer Res. 2012, 32, 847–860. [Google Scholar]
- Jager, M.J.; Magner, J.A.; Ksander, B.R.; Dubovy, S.R. Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis). Trans. Am. Ophthalmol. Soc. 2016, 114, T5. [Google Scholar] [PubMed]
- Onken, M.D.; Blumer, K.J.; Cooper, J.A. Uveal melanoma cells use ameboid and mesenchymal mechanisms of cell motility crossing the endothelium. Mol. Biol. Cell 2021, 32, 413–421. [Google Scholar] [CrossRef]
- Crosas-Molist, E.; Bertran, E.; Rodriguez-Hernandez, I.; Herraiz, C.; Cantelli, G.; Fabra, A.; Sanz-Moreno, V.; Fabregat, I. The NADPH oxidase NOX4 represses epithelial to amoeboid transition and efficient tumour dissemination. Oncogene 2017, 36, 3002–3014. [Google Scholar] [CrossRef]
- Liang, J.; Oyang, L.; Rao, S.; Han, Y.; Luo, X.; Yi, P.; Lin, J.; Xia, L.; Hu, J.; Tan, S.; et al. Rac1, A Potential Target for Tumor Therapy. Front. Oncol. 2021, 11, 674426. [Google Scholar] [CrossRef]
- Haga, R.B.; Ridley, A.J. Rho GTPases: Regulation and roles in cancer cell biology. Small GTPases 2016, 7, 207–221. [Google Scholar] [CrossRef]
- Sanz-Moreno, V.; Gadea, G.; Ahn, J.; Paterson, H.; Marra, P.; Pinner, S.; Sahai, E.; Marshall, C.J. Rac activation and inactivation control plasticity of tumor cell movement. Cell 2008, 135, 510–523. [Google Scholar] [CrossRef]
- Gabbireddy, S.R.; Vosatka, K.W.; Chung, A.J.; Logue, J.S. Melanoma cells adopt features of both mesenchymal and amoeboid migration within confining channels. Sci. Rep. 2021, 11, 17804. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.J.; Le Berre, M.; Lautenschlaeger, F.; Maiuri, P.; Callan-Jones, A.; Heuze, M.; Takaki, T.; Voituriez, R.; Piel, M. Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells. Cell 2015, 160, 659–672. [Google Scholar] [CrossRef] [PubMed]
- Hoshino, A.; Costa-Silva, B.; Shen, T.L.; Rodrigues, G.; Hashimoto, A.; Tesic Mark, M.; Molina, H.; Kohsaka, S.; Di Giannatale, A.; Ceder, S.; et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015, 527, 329–335. [Google Scholar] [CrossRef]
- Eligini, S.; Crisci, M.; Bono, E.; Songia, P.; Tremoli, E.; Colombo, G.I.; Colli, S. Human monocyte-derived macrophages spontaneously differentiated in vitro show distinct phenotypes. J. Cell Physiol. 2013, 228, 1464–1472. [Google Scholar] [CrossRef]
- Baig, M.S.; Roy, A.; Rajpoot, S.; Liu, D.; Savai, R.; Banerjee, S.; Kawada, M.; Faisal, S.M.; Saluja, R.; Saqib, U.; et al. Tumor-derived exosomes in the regulation of macrophage polarization. Inflamm. Res. 2020, 69, 435–451. [Google Scholar] [CrossRef]
- Linton, S.S.; Abraham, T.; Liao, J.; Clawson, G.A.; Butler, P.J.; Fox, T.; Kester, M.; Matters, G.L. Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages. PLoS ONE 2018, 13, e0206759. [Google Scholar] [CrossRef] [PubMed]
- Kang, N.; Gores, G.J.; Shah, V.H. Hepatic stellate cells: Partners in crime for liver metastases? Hepatology 2011, 54, 707–713. [Google Scholar] [CrossRef]
- Marvin, D.L.; Heijboer, R.; Ten Dijke, P.; Ritsma, L. TGF-beta signaling in liver metastasis. Clin. Transl. Med. 2020, 10, e160. [Google Scholar] [CrossRef]
- Su, X.; Ma, X.; Xie, X.; Wu, H.; Wang, L.; Feng, Y.; Yu, Z.; Liu, C.; Qi, J.; Zhu, Q. FN-EDA mediates angiogenesis of hepatic fibrosis via integrin-VEGFR2 in a CD63 synergetic manner. Cell Death Discov. 2020, 6, 140. [Google Scholar] [CrossRef] [PubMed]
- Kong, X.; Horiguchi, N.; Mori, M.; Gao, B. Cytokines and STATs in Liver Fibrosis. Front. Physiol. 2012, 3, 69. [Google Scholar] [CrossRef]
- Lotvall, J.; Hill, A.F.; Hochberg, F.; Buzas, E.I.; Di Vizio, D.; Gardiner, C.; Gho, Y.S.; Kurochkin, I.V.; Mathivanan, S.; Quesenberry, P.; et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles 2014, 3, 26913. [Google Scholar] [CrossRef]
- Boussadia, Z.; Lamberti, J.; Mattei, F.; Pizzi, E.; Puglisi, R.; Zanetti, C.; Pasquini, L.; Fratini, F.; Fantozzi, L.; Felicetti, F.; et al. Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J. Exp. Clin. Cancer Res. 2018, 37, 245. [Google Scholar] [CrossRef] [PubMed]
- Cooper, J.A.; Schafer, D.A. Control of actin assembly and disassembly at filament ends. Curr. Opin. Cell Biol. 2000, 12, 97–103. [Google Scholar] [CrossRef] [PubMed]
- Ridley, A.J.; Schwartz, M.A.; Burridge, K.; Firtel, R.A.; Ginsberg, M.H.; Borisy, G.; Parsons, J.T.; Horwitz, A.R. Cell migration: Integrating signals from front to back. Science 2003, 302, 1704–1709. [Google Scholar] [CrossRef] [PubMed]
- Sahai, E.; Marshall, C.J. RHO-GTPases and cancer. Nat. Rev. Cancer 2002, 2, 133–142. [Google Scholar] [CrossRef]
- Maacha, S.; Anezo, O.; Foy, M.; Liot, G.; Mery, L.; Laurent, C.; Sastre-Garau, X.; Piperno-Neumann, S.; Cassoux, N.; Planque, N.; et al. Protein Tyrosine Phosphatase 4A3 (PTP4A3) Promotes Human Uveal Melanoma Aggressiveness Through Membrane Accumulation of Matrix Metalloproteinase 14 (MMP14). Investig. Ophthalmol. Vis. Sci. 2016, 57, 1982–1990. [Google Scholar] [CrossRef]
- Watanabe, A.; Hoshino, D.; Koshikawa, N.; Seiki, M.; Suzuki, T.; Ichikawa, K. Critical role of transient activity of MT1-MMP for ECM degradation in invadopodia. PLoS Comput. Biol. 2013, 9, e1003086. [Google Scholar] [CrossRef]
- Sacharidou, A.; Koh, W.; Stratman, A.N.; Mayo, A.M.; Fisher, K.E.; Davis, G.E. Endothelial lumen signaling complexes control 3D matrix-specific tubulogenesis through interdependent Cdc42- and MT1-MMP-mediated events. Blood 2010, 115, 5259–5269. [Google Scholar] [CrossRef]
- Zhuge, Y.; Xu, J. Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier. J. Biol. Chem. 2001, 276, 16248–16256. [Google Scholar] [CrossRef]
- Lehtimaki, J.; Hakala, M.; Lappalainen, P. Actin Filament Structures in Migrating Cells. Handb. Exp. Pharmacol. 2017, 235, 123–152. [Google Scholar]
- Parri, M.; Chiarugi, P. Rac and Rho GTPases in cancer cell motility control. Cell Commun. Signal 2010, 8, 23. [Google Scholar] [CrossRef] [PubMed]
- Goicoechea, S.M.; Zinn, A.; Awadia, S.S.; Snyder, K.; Garcia-Mata, R. A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells. J. Cell Sci. 2017, 130, 1064–1077. [Google Scholar] [CrossRef] [PubMed]
- Brown, M.D.; Sacks, D.B. IQGAP1 in cellular signaling: Bridging the GAP. Trends Cell Biol. 2006, 16, 242–249. [Google Scholar] [CrossRef]
- Sedgwick, A.E.; Clancy, J.W.; Olivia Balmert, M.; D’Souza-Schorey, C. Extracellular microvesicles and invadopodia mediate non-overlapping modes of tumor cell invasion. Sci. Rep. 2015, 5, 14748. [Google Scholar] [CrossRef] [PubMed]
- Guilluy, C.; Dubash, A.D.; Garcia-Mata, R. Analysis of RhoA and Rho GEF activity in whole cells and the cell nucleus. Nat. Protoc. 2011, 6, 2050–2060. [Google Scholar] [CrossRef] [PubMed]
- Colletti, M.; Petretto, A.; Galardi, A.; Di Paolo, V.; Tomao, L.; Lavarello, C.; Inglese, E.; Bruschi, M.; Lopez, A.A.; Pascucci, L.; et al. Proteomic Analysis of Neuroblastoma-Derived Exosomes. New Insights into a Metastatic Signature. Proteomics 2017, 17, 1600430. [Google Scholar] [CrossRef] [PubMed]
- Schillaci, O.; Fontana, S.; Monteleone, F.; Taverna, S.; Di Bella, M.A.; Di Vizio, D.; Alessandro, R. Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: Their emerging role in tumor heterogeneity. Sci. Rep. 2017, 7, 4711. [Google Scholar] [CrossRef]
- Pourjafar, M.; Tiwari, V.K. Plasticity in cell migration modes across development, physiology, and disease. Front. Cell Dev. Biol. 2024, 12, 1363361. [Google Scholar] [CrossRef]
- Doherty, R.E.; Sisley, K.; Hammond, D.W.; Rennie, I.G.; Cross, N.A. Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics. Investig. Ophthalmol. Vis. Sci. 2017, 58, 5387–5395. [Google Scholar] [CrossRef]
- Weems, A.D.; Welf, E.S.; Driscoll, M.K.; Zhou, F.Y.; Mazloom-Farsibaf, H.; Chang, B.J.; Murali, V.S.; Gihana, G.M.; Weiss, B.G.; Chi, J.; et al. Blebs promote cell survival by assembling oncogenic signalling hubs. Nature 2023, 615, 517–525. [Google Scholar] [CrossRef]
- Sung, B.H.; Ketova, T.; Hoshino, D.; Zijlstra, A.; Weaver, A.M. Directional cell movement through tissues is controlled by exosome secretion. Nat. Commun. 2015, 6, 7164. [Google Scholar] [CrossRef] [PubMed]
- Aleem, E.; Berthet, C.; Kaldis, P. Cdk2 as a master of S phase entry: Fact or fake? Cell Cycle 2004, 3, 35–37. [Google Scholar] [CrossRef]
- Pozo, K.; Bibb, J.A. The Emerging Role of Cdk5 in Cancer. Trends Cancer 2016, 2, 606–618. [Google Scholar] [CrossRef]
- Suesskind, D.; Schatz, A.; Schnichels, S.; Coupland, S.E.; Lake, S.L.; Wissinger, B.; Bartz-Schmidt, K.U.; Henke-Fahle, S. GDF-15: A novel serum marker for metastases in uveal melanoma patients. Graefes Arch. Clin. Exp. Ophthalmol. 2012, 250, 887–895. [Google Scholar] [CrossRef] [PubMed]
- Rambow, F.; Job, B.; Petit, V.; Gesbert, F.; Delmas, V.; Seberg, H.; Meurice, G.; Van Otterloo, E.; Dessen, P.; Robert, C.; et al. New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis. Cell Rep. 2015, 13, 840–853. [Google Scholar] [CrossRef] [PubMed]
- Trussart, C.; Pirlot, C.; Di Valentin, E.; Piette, J.; Habraken, Y. Melanoma antigen-D2 controls cell cycle progression and modulates the DNA damage response. Biochem. Pharmacol. 2018, 153, 217–229. [Google Scholar] [CrossRef]
- Kuriyama, H.; Fukushima, S.; Kimura, T.; Okada, E.; Ishibashi, T.; Mizuhashi, S.; Kanemaru, H.; Kajihara, I.; Makino, K.; Miyashita, A.; et al. Matrin-3 plays an important role in cell cycle and apoptosis for survival in malignant melanoma. J. Dermatol. Sci. 2020, 100, 110–119. [Google Scholar] [CrossRef]
- Silva, P.M.A.; Bousbaa, H. BUB3, beyond the Simple Role of Partner. Pharmaceutics 2022, 14, 1084. [Google Scholar] [CrossRef]
- Abou-Hamad, J.; Hodgins, J.J.; de Souza, C.T.; Garland, B.; Labreche, C.; Marotel, M.; Gibson, C.; Delisle, S.; Pascoal, J.; Auer, R.C.; et al. CEACAM1 is a direct SOX10 target and inhibits melanoma immune infiltration and stemness. iScience 2022, 25, 105524. [Google Scholar] [CrossRef]
- Erdrich, J.; Lourdault, K.; Judd, A.; Kaufman, D.; Gong, K.W.; Gainsbury, M.; Deng, N.; Shon, W.; Essner, R. Four Immune Modulating Genes in Primary Melanoma That Predict Metastatic Potential. J. Surg. Res. 2022, 279, 682–691. [Google Scholar] [CrossRef]
- Arena, G.O.; Forte, S.; Abdouh, M.; Vanier, C.; Corbeil, D.; Lorico, A. Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis. Cells 2023, 12, 1566. [Google Scholar] [CrossRef]
- Piquet, L.; Coutant, K.; Mitchell, A.; Ben Anes, A.; Bollmann, E.; Schoonjans, N.; Berube, J.; Bordeleau, F.; Brisson, A.; Landreville, S. Extracellular Vesicles from Ocular Melanoma Have Pro-Fibrotic and Pro-Angiogenic Properties on the Tumor Microenvironment. Cells 2022, 11, 3828. [Google Scholar] [CrossRef]
- Populo, H.; Vinagre, J.; Lopes, J.M.; Soares, P. Analysis of GNAQ mutations, proliferation and MAPK pathway activation in uveal melanomas. Br. J. Ophthalmol. 2011, 95, 715–719. [Google Scholar] [CrossRef]
- Babchia, N.; Landreville, S.; Clement, B.; Coulouarn, C.; Mouriaux, F. The bidirectional crosstalk between metastatic uveal melanoma cells and hepatic stellate cells engenders an inflammatory microenvironment. Exp. Eye Res. 2019, 181, 213–222. [Google Scholar] [CrossRef] [PubMed]
- Bardi, G.T.; Smith, M.A.; Hood, J.L. Melanoma exosomes promote mixed M1 and M2 macrophage polarization. Cytokine 2018, 105, 63–72. [Google Scholar] [CrossRef] [PubMed]
- Caja, L.; Dituri, F.; Mancarella, S.; Caballero-Diaz, D.; Moustakas, A.; Giannelli, G.; Fabregat, I. TGF-beta and the Tissue Microenvironment: Relevance in Fibrosis and Cancer. Int. J. Mol. Sci. 2018, 19, 1294. [Google Scholar] [CrossRef] [PubMed]
- Fabregat, I.; Caballero-Diaz, D. Transforming Growth Factor-beta-Induced Cell Plasticity in Liver Fibrosis and Hepatocarcinogenesis. Front. Oncol. 2018, 8, 357. [Google Scholar] [CrossRef] [PubMed]
- Masamune, A.; Yoshida, N.; Hamada, S.; Takikawa, T.; Nabeshima, T.; Shimosegawa, T. Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells. Biochem. Biophys. Res. Commun. 2018, 495, 71–77. [Google Scholar] [CrossRef]
- Chang, C.J.; Hsu, L.A.; Ko, Y.H.; Chen, P.L.; Chuang, Y.T.; Lin, C.Y.; Liao, C.H.; Pang, J.H.S. Thrombin regulates matrix metalloproteinase-9 expression in human monocytes. Biochem. Biophys. Res. Commun. 2009, 385, 241–246. [Google Scholar] [CrossRef]
- Lafleur, M.A.; Hollenberg, M.D.; Atkinson, S.J.; Knäuper, V.; Murphy, G.; Edwards, D.R. Activation of pro-(matrix metalloproteinase-2)(pro-MMP-2) by thrombin is membrane-type-MMP-dependent in human umbilical vein endothelial cells and generates a distinct 63 kDa active species. Biochem. J. 2001, 357, 107–115. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ramos, R.; Vinyals, A.; Campos-Martin, R.; Cabré, E.; Bech, J.J.; Vaquero, J.; Gonzalez-Sanchez, E.; Bertran, E.; Ferreres, J.R.; Lorenzo, D.; et al. New Insights into the Exosome-Induced Migration of Uveal Melanoma Cells and the Pre-Metastatic Niche Formation in the Liver. Cancers 2024, 16, 2977. https://doi.org/10.3390/cancers16172977
Ramos R, Vinyals A, Campos-Martin R, Cabré E, Bech JJ, Vaquero J, Gonzalez-Sanchez E, Bertran E, Ferreres JR, Lorenzo D, et al. New Insights into the Exosome-Induced Migration of Uveal Melanoma Cells and the Pre-Metastatic Niche Formation in the Liver. Cancers. 2024; 16(17):2977. https://doi.org/10.3390/cancers16172977
Chicago/Turabian StyleRamos, Raquel, Antònia Vinyals, Rafael Campos-Martin, Eduard Cabré, Joan Josep Bech, Javier Vaquero, Ester Gonzalez-Sanchez, Esther Bertran, Josep Ramon Ferreres, Daniel Lorenzo, and et al. 2024. "New Insights into the Exosome-Induced Migration of Uveal Melanoma Cells and the Pre-Metastatic Niche Formation in the Liver" Cancers 16, no. 17: 2977. https://doi.org/10.3390/cancers16172977