Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells
BackgroundNumerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM),...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.918340/full |
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| author | Khuloud Bajbouj Khuloud Bajbouj Abeer Al-Ali Jasmin Shafarin Lina Sahnoon Ahmad Sawan Ahmed Shehada Walaaeldin Elkhalifa Maha Saber-Ayad Maha Saber-Ayad Maha Saber-Ayad Jibran Sualeh Muhammad Jibran Sualeh Muhammad Adel B. Elmoselhi Adel B. Elmoselhi Adel B. Elmoselhi Salman Y. Guraya Salman Y. Guraya Mawieh Hamad Mawieh Hamad |
| author_facet | Khuloud Bajbouj Khuloud Bajbouj Abeer Al-Ali Jasmin Shafarin Lina Sahnoon Ahmad Sawan Ahmed Shehada Walaaeldin Elkhalifa Maha Saber-Ayad Maha Saber-Ayad Maha Saber-Ayad Jibran Sualeh Muhammad Jibran Sualeh Muhammad Adel B. Elmoselhi Adel B. Elmoselhi Adel B. Elmoselhi Salman Y. Guraya Salman Y. Guraya Mawieh Hamad Mawieh Hamad |
| author_sort | Khuloud Bajbouj |
| collection | DOAJ |
| description | BackgroundNumerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM), which represents the endothelial-independent formation of microvascular channels by cancer cells. However, the effect of vitamin D on VM formation in BC has not been thoroughly investigated. This study examined the impact of 1α,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, on the expression of major factors involved in BC migration, invasion, and VM formation.Experimental MethodsPublicly available transcriptomic datasets were used to profile the expression status of the key VM markers in vitamin D-treated BC cells. The in silico data were validated by examining the expression and activity of the key factors that are involved in tumor progression and MV formation in hormone-positive MCF-7 and aggressive triple‐negative MDA-MB-231 BC cells after treatment with calcitriol.Results and DiscussionsThe bioinformatics analysis showed that tumor VM formation-enriched pathways were differentially downregulated in vitamin D-treated cells when compared with control counterparts. Treatment of BC cells with calcitriol resulted in increased expression of tissue inhibitors of metalloproteinases (TIMPs 1 and 2) and decreased content and gelatinolytic activity of matrix metalloproteinases (MMPs 2 and 9). Furthermore, calcitriol treatment reduced the expression of several pro-MV formation regulators including vascular endothelial growth factor (VEGF), tumor growth factor (TGF-β1), and amphiregulin. Eventually, this process resulted in a profound reduction in cell migration and invasion following the treatment of BC cells with calcitriol when compared to the controls. Finally, the formation of VM was diminished in the aggressive triple‐negative MDA-MB-231 cancer cell line after calcitriol treatment.ConclusionOur findings demonstrate that vitamin D mediates its antitumor effects in BC cells by inhibiting and curtailing their potential for VM formation. |
| first_indexed | 2024-12-11T17:58:26Z |
| format | Article |
| id | doaj.art-b2bb14ba6f3140dcb1a300d517f50996 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T17:58:26Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b2bb14ba6f3140dcb1a300d517f509962022-12-22T00:55:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.918340918340Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer CellsKhuloud Bajbouj0Khuloud Bajbouj1Abeer Al-Ali2Jasmin Shafarin3Lina Sahnoon4Ahmad Sawan5Ahmed Shehada6Walaaeldin Elkhalifa7Maha Saber-Ayad8Maha Saber-Ayad9Maha Saber-Ayad10Jibran Sualeh Muhammad11Jibran Sualeh Muhammad12Adel B. Elmoselhi13Adel B. Elmoselhi14Adel B. Elmoselhi15Salman Y. Guraya16Salman Y. Guraya17Mawieh Hamad18Mawieh Hamad19College of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesMedical Pharmacology Department, Cairo University, Cairo, EgyptCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Physiology, Michigan State University, East Lansing, MI, United StatesCollege of Medicine, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab EmiratesCollege of Health Sciences, University of Sharjah, Sharjah, United Arab EmiratesBackgroundNumerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM), which represents the endothelial-independent formation of microvascular channels by cancer cells. However, the effect of vitamin D on VM formation in BC has not been thoroughly investigated. This study examined the impact of 1α,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, on the expression of major factors involved in BC migration, invasion, and VM formation.Experimental MethodsPublicly available transcriptomic datasets were used to profile the expression status of the key VM markers in vitamin D-treated BC cells. The in silico data were validated by examining the expression and activity of the key factors that are involved in tumor progression and MV formation in hormone-positive MCF-7 and aggressive triple‐negative MDA-MB-231 BC cells after treatment with calcitriol.Results and DiscussionsThe bioinformatics analysis showed that tumor VM formation-enriched pathways were differentially downregulated in vitamin D-treated cells when compared with control counterparts. Treatment of BC cells with calcitriol resulted in increased expression of tissue inhibitors of metalloproteinases (TIMPs 1 and 2) and decreased content and gelatinolytic activity of matrix metalloproteinases (MMPs 2 and 9). Furthermore, calcitriol treatment reduced the expression of several pro-MV formation regulators including vascular endothelial growth factor (VEGF), tumor growth factor (TGF-β1), and amphiregulin. Eventually, this process resulted in a profound reduction in cell migration and invasion following the treatment of BC cells with calcitriol when compared to the controls. Finally, the formation of VM was diminished in the aggressive triple‐negative MDA-MB-231 cancer cell line after calcitriol treatment.ConclusionOur findings demonstrate that vitamin D mediates its antitumor effects in BC cells by inhibiting and curtailing their potential for VM formation.https://www.frontiersin.org/articles/10.3389/fonc.2022.918340/fullvitamin Dbreast cancerinvasionvasculogenic mimicrymetalloproteinases |
| spellingShingle | Khuloud Bajbouj Khuloud Bajbouj Abeer Al-Ali Jasmin Shafarin Lina Sahnoon Ahmad Sawan Ahmed Shehada Walaaeldin Elkhalifa Maha Saber-Ayad Maha Saber-Ayad Maha Saber-Ayad Jibran Sualeh Muhammad Jibran Sualeh Muhammad Adel B. Elmoselhi Adel B. Elmoselhi Adel B. Elmoselhi Salman Y. Guraya Salman Y. Guraya Mawieh Hamad Mawieh Hamad Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells Frontiers in Oncology vitamin D breast cancer invasion vasculogenic mimicry metalloproteinases |
| title | Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells |
| title_full | Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells |
| title_fullStr | Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells |
| title_full_unstemmed | Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells |
| title_short | Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells |
| title_sort | vitamin d exerts significant antitumor effects by suppressing vasculogenic mimicry in breast cancer cells |
| topic | vitamin D breast cancer invasion vasculogenic mimicry metalloproteinases |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.918340/full |
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