Melanoma-derived Extracellular Vesicles Transfer Proangiogenic Factors

Overview

Journal Oncol Res

Date 2025 Jan 27

PMID 39866233

Authors

Magdalena Wilczak

Magdalena Surman

MAlGORZATA PRZYBYlO

Affiliations

Soon will be listed here.

Abstract

Angiogenesis, the expansion of pre-existing vascular networks, is crucial for normal organ growth and tissue repair, but is also involved in various pathologies, including inflammation, ischemia, diabetes, and cancer. In solid tumors, angiogenesis supports growth, nutrient delivery, waste removal, and metastasis. Tumors can induce angiogenesis through proangiogenic factors including VEGF, FGF-2, PDGF, angiopoietins, HGF, TNF, IL-6, SCF, tryptase, and chymase. This balance is disrupted in tumors, and extracellular vesicles (EVs) contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells (ECs). Malignant melanoma, a particular type of skin cancer, accounts for only 1% of skin cancer cases but more than 75% of deaths. Its incidence has risen significantly, with a 40% increase between 2012 and 2022, especially in fair-skinned populations. Advanced metastatic stages have a high mortality due to delayed diagnosis. This review examines the molecular basis of angiogenesis in melanoma, focusing on melanoma-derived EVs and their possible use in new antiangiogenic therapies.

References

Streit S, Mestel D, Schmidt M, Ullrich A, Berking C . FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients. Br J Cancer. 2006; 94(12):1879-86. PMC: 2361343. DOI: 10.1038/sj.bjc.6603181. View

Zhou Q, Fang T, Wei S, Chai S, Yang H, Tao M . Macrophages in melanoma: A double‑edged sword and targeted therapy strategies (Review). Exp Ther Med. 2022; 24(4):640. PMC: 9468802. DOI: 10.3892/etm.2022.11577. View

Forsberg K, Valyi-Nagy I, Heldin C, Herlyn M, Westermark B . Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB. Proc Natl Acad Sci U S A. 1993; 90(2):393-7. PMC: 45668. DOI: 10.1073/pnas.90.2.393. View

Parikh R, Parikh S, Berzin D, Vaknine H, Ovadia S, Likonen D . Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification. EMBO J. 2024; 43(17):3553-3586. PMC: 11377571. DOI: 10.1038/s44318-024-00103-7. View

Tarhini A, Frankel P, Ruel C, Ernstoff M, Kuzel T, Logan T . NCI 8628: A randomized phase 2 study of ziv-aflibercept and high-dose interleukin 2 or high-dose interleukin 2 alone for inoperable stage III or IV melanoma. Cancer. 2018; 124(22):4332-4341. PMC: 6504933. DOI: 10.1002/cncr.31734. View

Ruffini F, Levati L, Graziani G, Caporali S, Atzori M, DAtri S . Platelet-derived growth factor-C promotes human melanoma aggressiveness through activation of neuropilin-1. Oncotarget. 2017; 8(40):66833-66848. PMC: 5620139. DOI: 10.18632/oncotarget.18706. View

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(2):72. DOI: 10.31083/j.fbl2702072. View

Tang F, Li S, Liu D, Chen J, Han C . Sorafenib sensitizes melanoma cells to vemurafenib through ferroptosis. Transl Cancer Res. 2022; 9(3):1584-1593. PMC: 8798636. DOI: 10.21037/tcr.2020.01.62. View

Takeda T, Tsubaki M, Kato N, Genno S, Ichimura E, Enomoto A . Sorafenib treatment of metastatic melanoma with c-Kit aberration reduces tumor growth and promotes survival. Oncol Lett. 2021; 22(6):827. PMC: 8527568. DOI: 10.3892/ol.2021.13089. View

10.

Kosgodage U, Trindade R, Thompson P, Inal J, Lange S . Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition of Exosome and Microvesicle Release and Enhanced Efficacy of Cancer Chemotherapy. Int J Mol Sci. 2017; 18(5). PMC: 5454920. DOI: 10.3390/ijms18051007. View

11.

van Belle P, Rodeck U, Nuamah I, Halpern A, Elder D . Melanoma-associated expression of transforming growth factor-beta isoforms. Am J Pathol. 1996; 148(6):1887-94. PMC: 1861638. View

12.

Moller A, Lobb R . The evolving translational potential of small extracellular vesicles in cancer. Nat Rev Cancer. 2020; 20(12):697-709. DOI: 10.1038/s41568-020-00299-w. View

13.

Rothhammer T, Bataille F, Spruss T, Eissner G, Bosserhoff A . Functional implication of BMP4 expression on angiogenesis in malignant melanoma. Oncogene. 2006; 26(28):4158-70. DOI: 10.1038/sj.onc.1210182. View

14.

Mahabeleshwar G, Byzova T . Angiogenesis in melanoma. Semin Oncol. 2007; 34(6):555-65. PMC: 2365306. DOI: 10.1053/j.seminoncol.2007.09.009. View

15.

Robinson S, Ludwig C, Paulsson J, Ostman A . The effects of tumor-derived platelet-derived growth factor on vascular morphology and function in vivo revealed by susceptibility MRI. Int J Cancer. 2007; 122(7):1548-56. DOI: 10.1002/ijc.23279. View

16.

Dayer L, Hutchins L, Johnson J . Treatment of metastatic melanoma with pazopanib: A report of five patient cases. J Oncol Pharm Pract. 2014; 21(3):224-31. DOI: 10.1177/1078155214524084. View

17.

Parmar D, Apte M . Angiopoietin inhibitors: A review on targeting tumor angiogenesis. Eur J Pharmacol. 2021; 899:174021. DOI: 10.1016/j.ejphar.2021.174021. View

18.

Hosaka K, Yang Y, Nakamura M, Andersson P, Yang X, Zhang Y . Dual roles of endothelial FGF-2-FGFR1-PDGF-BB and perivascular FGF-2-FGFR2-PDGFRβ signaling pathways in tumor vascular remodeling. Cell Discov. 2018; 4:3. PMC: 5798893. DOI: 10.1038/s41421-017-0002-1. View

19.

Lima L, Oliveira A, Campos L, Bonamino M, Chammas R, Werneck C . Malignant transformation in melanocytes is associated with increased production of procoagulant microvesicles. Thromb Haemost. 2011; 106(4):712-23. DOI: 10.1160/TH11-03-0143. View

20.

Arance A, de la Cruz-Merino L, Petrella T, Jamal R, Ny L, Carneiro A . Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. J Clin Oncol. 2022; 41(1):75-85. DOI: 10.1200/JCO.22.00221. View