ECM1 secreted by HER2-overexpressing breast cancer cells promotes formation of a vascular niche accelerating cancer cell migration and invasion.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsSteinhaeuser, Sophie Sarah
Maelandsmo, Gunhild Mari
Sigurdardottir, Anna Karen
Agnarsson, Bjarni Agnar
Jonasson, Jon Gunnlaugur
Traustadottir, Gunnhildur Asta
MetadataShow full item record
CitationSteinhaeuser SS, Morera E, Budkova Z, et al. ECM1 secreted by HER2-overexpressing breast cancer cells promotes formation of a vascular niche accelerating cancer cell migration and invasion [published online ahead of print, 2020 Mar 18]. Lab Invest. 2020;10.1038/s41374-020-0415-6. doi:10.1038/s41374-020-0415-6
ÚtdrátturThe tumor microenvironment is increasingly recognized as key player in cancer progression. Investigating heterotypic interactions between cancer cells and their microenvironment is important for understanding how specific cell types support cancer. Forming the vasculature, endothelial cells (ECs) are a prominent cell type in the microenvironment of both normal and neoplastic breast gland. Here, we sought out to analyze epithelial-endothelial cross talk in the breast using isogenic non-tumorigenic vs. tumorigenic breast epithelial cell lines and primary ECs. The cellular model used here consists of D492, a breast epithelial cell line with stem cell properties, and two isogenic D492-derived EMT cell lines, D492M and D492HER2. D492M was generated by endothelial-induced EMT and is non-tumorigenic while D492HER2 is tumorigenic, expressing the ErbB2/HER2 oncogene. To investigate cellular cross talk, we used both conditioned medium (CM) and 2D/3D co-culture systems. Secretome analysis of D492 cell lines was performed using mass spectrometry and candidate knockdown (KD), and overexpression (OE) was done using siRNA and CRISPRi/CRISPRa technology. D492HER2 directly enhances endothelial network formation and activates a molecular axis in ECs promoting D492HER2 migration and invasion, suggesting an endothelial feedback response. Secretome analysis identified extracellular matrix protein 1 (ECM1) as potential angiogenic inducer in D492HER2. Confirming its involvement, KD of ECM1 reduced the ability of D492HER2-CM to increase endothelial network formation and induce the endothelial feedback, while recombinant ECM1 (rECM1) increased both. Interestingly, NOTCH1 and NOTCH3 expression was upregulated in ECs upon treatment with D492HER2-CM or rECM1 but not by CM from D492HER2 with ECM1 KD. Blocking endothelial NOTCH signaling inhibited the increase in network formation and the ability of ECs to promote D492HER2 migration and invasion. In summary, our data demonstrate that cancer-secreted ECM1 induces a NOTCH-mediated endothelial feedback promoting cancer progression by enhancing migration and invasion. Targeting this interaction may provide a novel possibility to improve cancer treatment.
Lu00FDsingTo access publisher's full text version of this article click on the hyperlink below
- YKL-40/CHI3L1 facilitates migration and invasion in HER2 overexpressing breast epithelial progenitor cells and generates a niche for capillary-like network formation.
- Authors: Morera E, Steinhäuser SS, Budkova Z, Ingthorsson S, Kricker J, Krueger A, Traustadottir GA, Gudjonsson T
- Issue date: 2019 Dec
- Extracellular matrix 1 (ECM1) regulates the actin cytoskeletal architecture of aggressive breast cancer cells in part via S100A4 and Rho-family GTPases.
- Authors: Gómez-Contreras P, Ramiro-Díaz JM, Sierra A, Stipp C, Domann FE, Weigel RJ, Lal G
- Issue date: 2017 Jan
- Breast cancer cells promote a notch-dependent mesenchymal phenotype in endothelial cells participating to a pro-tumoral niche.
- Authors: Ghiabi P, Jiang J, Pasquier J, Maleki M, Abu-Kaoud N, Halabi N, Guerrouahen BS, Rafii S, Rafii A
- Issue date: 2015 Jan 27
- Extracellular matrix protein 1 recruits moesin to facilitate invadopodia formation and breast cancer metastasis.
- Authors: Wu Q, Chen D, Luo Q, Yang Q, Zhao C, Zhang D, Zeng Y, Huang L, Zhang Z, Qi Z
- Issue date: 2018 Nov 28
- Upregulation of MIIP regulates human breast cancer proliferation, invasion and migration by mediated by IGFBP2.
- Authors: Du Y, Wang P
- Issue date: 2019 Jul