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Stem-like Human Breast Cancer Cells Initiate Vasculogenic Mimicry on Matrigel.

ABSTRACT: Vasculogenic mimicry (VM), referring to vasculogenic structures lined by tumor cells, can be distinguished from angiogenesis, and is responsible for the aggressiveness and metastatic potential of tumors. HCC1937/p53 cells were derived from triple-negative breast cancer (TNBC), and used to investigate the roles of breast cancer stem cells (CSCs) in the formation of VM. HCC1937/p53 cells formed mesh-like structures on matrigel culture in which expression of VM-related genes, vascular endothelial (VE)-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9 was confirmed by droplet digital polymerase chain reaction (PCR). In immunofluorescence microscopy, aldehyde dehydrogenase (ALDH)1A3⁺ cells with properties of CSCs or progenitors and GATA binding protein 3 (GATA3)⁺ cells with more differentiated characteristics were localized in the bridging region and aggregated region of VM structures, respectively. In fluorescence-activated cell sorting analysis, ALDH⁺ cells, considered to be a subpopulation of CSCs sorted by the aldefluor assay, exhibited marked VM formation on matrigel in 24 hr, whereas ALDH^- cells did not form VM, indicating possible roles of CSCs in VM formation. The stem-like cancer cells resistant to p53-induced apoptosis, which expressed a high rate of ALDH1A3 and Sex-determining region Y (SRY)-box binding protein-2 (Sox-2), completed VM formation much faster than the control. These findings may provide clues to elucidate the significance of VM formed by treatment-resistant CSCs in the metastatic potential and poor prognosis associated with TNBC.

SUBMITTER: Izawa Y

PROVIDER: S-EPMC6328367 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Stem-like Human Breast Cancer Cells Initiate Vasculogenic Mimicry on Matrigel.

Izawa Yuki Y Kashii-Magaribuchi Karin K Yoshida Kana K Nosaka Mayu M Tsuji Nanami N Yamamoto Ai A Kuroyanagi Kana K Tono Kanoko K Tanihata Misato M Imanishi Moe M Onishi Momoka M Sakiyama Mayu M Inoue Sana S Takahashi Rei R

Acta histochemica et cytochemica 20181215 6

Vasculogenic mimicry (VM), referring to vasculogenic structures lined by tumor cells, can be distinguished from angiogenesis, and is responsible for the aggressiveness and metastatic potential of tumors. HCC1937/p53 cells were derived from triple-negative breast cancer (TNBC), and used to investigate the roles of breast cancer stem cells (CSCs) in the formation of VM. HCC1937/p53 cells formed mesh-like structures on matrigel culture in which expression of VM-related genes, vascular endothelial ( ...[more]

PMID: 30647492

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Project description:Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.

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Stem-like Human Breast Cancer Cells Initiate Vasculogenic Mimicry on Matrigel.

Publications

Stem-like Human Breast Cancer Cells Initiate Vasculogenic Mimicry on Matrigel.

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