Investigating the role of CRIPTO-1 (TDGF-1) in glioblastoma multiforme U87 cell line |
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Authors: | Faisal Alowaidi Saeed M Hashimi Maria Nguyen Mallika Meshram Naif Alqurashi Brenton L Cavanagh Bernadette Bellette Saso Ivanovski Adrian Meedenyia Stephen A Wood |
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Affiliation: | 1. Department of Pathology and Laboratory Medicine, College of Medicine and University Hospitals, King Saud University, Riyadh, Saudi Arabia Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland, Australia;2. Department of Basic Science, Biology Unit, Deanship of Preparatory Year and Supporting studies, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia;3. Griffith Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia;4. Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland, Australia |
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Abstract: | Cripto-1 has been implicated in a number of human cancers. Although there is high potential for a role of Cripto-1 in glioblastoma multiforme (GBM) pathogenesis and progression, few studies have tried to define its role in GBM. These studies were limited in that Cripto-1 expression was not studied in detail in relation to markers of cancer initiation and progression. Therefore, these correlative studies allowed limited interpretation of Criptos-1's effect on the various aspects of GBM development using the U87 GBM cell line. In this study, we sought to delineate the role of Cripto-1 in facilitating pathogenesis, stemness, proliferation, invasion, migration and angiogenesis in GBM. Our findings show that upon overexpressing Cripto-1 in U87 GBM cells, the stemness markers Nanog, Oct4, Sox2, and CD44 increased expression. Similarly, an increase in Ki67 was observed demonstrating Cripto-1's potential to induce cellular proliferation. Likewise, we report a novel finding that increased expression of the markers of migration and invasion, Vimentin and Twist, correlated with upregulation of Cripto-1. Moreover, Cripto-1 exposure led to VEGFR-2 overexpression along with higher tube formation under conditions promoting endothelial growth. Taken together our results support a role for Cripto-1 in the initiation, development, progression, and maintenance of GBM pathogenesis. The data presented here are also consistent with a role for Cripto-1 in the re-growth and invasive growth in GBM. This highlights its potential use as a predictive and diagnostic marker in GBM as well as a therapeutic target. |
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Keywords: | CRIPTO-1 dedifferentiation epithelial to mesenchymal transition (EMT) proliferation vasculature |
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