ADAM12 Is a Novel Regulator of Tumor Angiogenesis via STAT3 Signaling

ADAM12, (A Disintegrin and metalloproteinase domain-containing protein 12), is upregulated in epithelial cancers and contributes to increased tumor proliferation, metastasis, and endocrine resistance. However, its role in tumor angiogenesis is unknown. Here, we report that ADAM12 is upregulated in the vessels of aggressive breast tumors and exerts key regulatory functions. ADAM12 significantly increases bFGF-mediated angiogenesis in vivo and ADAM12 levels are upregulated in tumors that have undergone a switch to the angiogenic phenotype. Importantly, ADAM12-overexpressing breast tumors display a higher microvessel density (MVD). Our goal was to identify the mechanisms by which tumor-associated ADAM12 promotes angiogenesis. ADAM12 expression in breast tumor cells correlated with a significant upregulation of proangiogenic factors such as VEGF and MMP-9 and downregulation of antiangiogenic factors such as Thrombospondin-1 (THBS1/TSP1) and Tissue Inhibitor of Metalloproteinases-2 (TIMP-2). Co-culture with ADAM12-expressing tumor cells promoted endothelial cell (EC) recruitment and capillary tube formation. Conversely, downregulation of endogenous ADAM12 in breast cancer cell lines resulted in reduction of pro-angiogenic factors and EC recruitment. These ADAM12-mediated effects are driven by the activation of EGFR, STAT3 and Akt signaling. Blockade of EGFR/STAT3 or silencing of ADAM12 reversed the proangiogenic tumor phenotype, significantly downregulated pro-angiogenic mitogens ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signal Transduction Source Type: research

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Contributors : Girieca Lorusso ; Curzio RueggSeries Type : Expression profiling by arrayOrganism : Mus musculusWe recently established an orthotopic breast cancer model of brain metastasis based on the injection of murine breast cancer cell lines into the mammary fat pad. This model is based on the use of 4T1 murine breast carcinoma cells. 4T1-derived tumors recapitulate the main steps of human breast cancer progression, including epithelial-to-mesenchymal transition and metastases to lung and lymph nodes.Bioluminescence imaging revealed the appearance of secondary lesions to the lung and lymph nodes and sporadically to th...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
rooks Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated wit...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ntamaria-Martinez Rüegg Membrane-associated guanylate kinase (MAGUK) with inverted domain structure-1 (MAGI1) is an intracellular adaptor protein that stabilizes epithelial junctions consistent with a tumor suppressive function in several cancers of epithelial origin. Here we report, based on experimental results and human breast cancer (BC) patients’ gene expression data, that MAGI1 is highly expressed and acts as tumor suppressor in estrogen receptor (ER)+/HER2− but not in HER2+ or triple negative breast cancer (TNBC). Within the ER+/HER2− subset, high MAGI1 expression associates...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: HDACi suppress the epithelial-mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells. PMID: 31932908 [PubMed - as supplied by publisher]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
ConclusionIn women with BBD, breast lobules with increasing epithelial abnormality show significant decreases in cytotoxic T cells as measured by CD8/CD103 staining, suggesting that impaired immunosurveillance may be a component of the earliest stages of breast cancer development.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ConclusionHDACi suppress the epithelial –mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 9 January 2020Source: Stem Cell ReportsAuthor(s): Raghava R. Sunkara, Rahul M. Sarate, Priyanka Setia, Sanket Shah, Sanjay Gupta, Pankaj Chaturvedi, Poonam Gera, Sanjeev K. WaghmareSummaryWnt signaling is involved in the regulation of cancer stem cells (CSCs); however, the molecular mechanism involved is still obscure. SFRP1, a Wnt inhibitor, is downregulated in various human cancers; however, its role in tumor initiation and CSC regulation remains unexplored. Here, we used a skin carcinogenesis model, which showed early tumor initiation in Sfrp1−/− (Sfrp1 knockout) mice and i...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Source: Cell Cycle - Category: Cytology Authors: Source Type: research
CONCLUSIONS: The differential diagnosis between OM and primary ovarian cancer can be challenging for the pathologist as well and immunostaining is of help. GCFDP15 is the most specific for breast carcinoma. In contrast with the recent papers published in the literature, we detected TTF-1 cytoplasmic expression in invasive breast carcinoma by SPT24 clone. PMID: 31912104 [PubMed - in process]
Source: Romanian Journal of Morphology and Embryology - Category: General Medicine Tags: Rom J Morphol Embryol Source Type: research
CONCLUSIONS: Taken together, miR-383-5p was downregulated in breast cancer tissues and cell lines, and overexpression of miR-383-5p inhibited cell proliferation, migration, and invasion in breast cancer cells by targeting LDHA. Based on our findings, miR-383-5p may be a prognostic biomarker and therapeutic target for breast cancer. PMID: 31903982 [PubMed - as supplied by publisher]
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
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