Project description:Vasculogenic mimicry has been generally accepted as a new form of tumor vascularization and regarded as an unfavorable prognostic factor in multiple aggressive malignancies. We previously reported the presence of vasculogenic mimicry in osteosarcoma patients. The mechanistic basis for osteosarcoma VM remains unclear. We used microarrays to detail the global programme of gene expression between 143B cells and HOS cells exposed to Matrigel which showed greatly different vasculogenic mimicry formation potential and identified distinct classes of vasculogenic mimicry-realted genes during this process.
Project description:Vasculogenic mimicry (VM) is an intriguing phenomenon observed in tumor masses, in which cancer cells organize themselves into capillary-like channels that closely resemble the structure and function of blood vessels. Although VM is believed to contribute to alternative tumor vascularization, the detailed regulatory mechanisms controlling these cellular processes remain poorly understood. Our study aimed to investigate the role of Early Growth Response 1 (EGR1) in regulating VM in aggressive cancer cells, specifically MDA-MB-231 triple-negative breast cancer cells.
Project description:The goal of this study was to determine the transcriptional changes associated with breast cancer cells undergoing vascular mimicry in a 3D assay. Two breast cancer cell lines were plated on matrigel in the presence or absence of serum. MDA-MB-231 cells undergo vascular mimicry on matrigel in the absence of serum, MDA-MB-453 cells do not.
Project description:Cancer vasculogenic mimicry (VM) is the formation of vasculature structures in the absence of endothelial cells. We previously established an in vitro model that facilitates the formation of a lumen-containing and fluid-conducting tubular structures after 4 days cancer cell growth on Matrigel. Herein, we mechanistically characterize this model in breast and ovarian cancer cell lines demonstrating distinct phases of VM formation and the dependence of specific extracellular matrix proteins. We report that VM occurs in four distinct stages. Firstly, alignment, migration then clustering delineate the area of the future tubular structure. Secondly, contraction of aligned structures followed by loss of attachment of some cells and cellular blebbing. Thirdly, a phase of mass proliferation followed by the raising of specific areas of the cancer cell mass above the Matrigel (bridge). Finally, the formation of a cell monolayer closes the tubular structure, forms a glycoprotein-rich luminal lining, then elevates the structure. Only later stages of VM require AKT and FAK signaling. We demonstrate that the lining of the tubular lumen is rich in laminin. Laminin 111 (but not collagen I) must be presence in the extracellular matrix (Matrigel) for VM to occur and integrin β1, but not integrin β3, is required. RNASeq demonstrates that formation is principally post-transcriptional regulation, however, this technique together with siRNA knockdown identified the first and essential biological function for the protein SMIM11A. VM is associated with poor patient survival and thus an understanding of the mechanism of VM may bring to light novel anticancer targets.