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https://hdl.handle.net/2440/133749
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Type: | Journal article |
Title: | CD36 promotes vasculogenic mimicry in melanoma by mediating adhesion to the extracellular matrix |
Author: | Martini, C. DeNichilo, M. King, D.P. Cockshell, M.P. Ebert, B. Dale, B. Ebert, L.M. Woods, A. Bonder, C.S. |
Citation: | BMC Cancer, 2021; 21(1):765-1-765-14 |
Publisher: | Springer Nature |
Issue Date: | 2021 |
ISSN: | 1471-2407 1471-2407 |
Statement of Responsibility: | Carmela Martini, Mark DeNichilo, Danielle P. King, Michaelia P. Cockshell, Brenton Ebert, Brian Dale, Lisa M. Ebert, Anthony Woods, and Claudine S. Bonder |
Abstract: | Background: The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as vasculogenic mimicry (VM). While it is generally understood that the function of VM vessels is the same as that of EC-lined vessels (i.e. to supply oxygen and nutrients to the proliferating cancer cells), the molecular mechanisms underpinning VM are yet to be fully elucidated. Methods: Human VM-competent melanoma cell lines were examined for their VM potential using the in vitro angiogenesis assays (Matrigel), together with inhibition studies using small interfering RNA and blocking monoclonal antibodies. Invasion assays and adhesion assays were used to examine cancer cell function. Results: Herein we demonstrate that CD36, a cell surface glycoprotein known to promote angiogenesis by ECs, also supports VM formation by human melanoma cancer cells. In silico analysis of CD36 expression within the melanoma cohort of The Cancer Genome Atlas suggests that melanoma patients with high expression of CD36 have a poorer clinical outcome. Using in vitro ‘angiogenesis’ assays and CD36-knockdown approaches, we reveal that CD36 supports VM formation by human melanoma cells as well as adhesion to, and invasion through, a cancer derived extracellular matrix substrate. Interestingly, thrombospondin-1 (TSP-1), a ligand for CD36 on ECs that inhibits angiogenesis, has no effect on VM formation. Further investigation revealed a role for laminin, but not collagen or fibronectin, as ligands for CD36 expressing melanoma cells. Conclusions: Taken together, this study suggests that CD36 is a novel regulator of VM by melanoma cancer cells that is facilitated, at least in part, via integrin-α3 and laminin. Unlike angiogenesis, VM is not perturbed by the presence of TSP-1, thus providing new information on differences between these two processes of tumor vascularization which may be exploited to combat cancer progression. |
Keywords: | CD36 Vasculogenic mimicry Melanoma Tumor microenvironment Thrombospondin Laminin Integrin |
Rights: | © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
DOI: | 10.1186/s12885-021-08482-4 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/GNT1022150 |
Published version: | http://dx.doi.org/10.1186/s12885-021-08482-4 |
Appears in Collections: | Medicine publications |
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hdl_133749.pdf | Published version | 4.38 MB | Adobe PDF | View/Open |
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