Twist1 induces CCL2 and recruits macrophages to promote angiogenesis
| Autor: | Nico van Rooijen, Edward A. Vizcarra, Jing Yang, Veronica C. Ardi, Janine M. Low-Marchelli, James P. Quigley |
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| Přispěvatelé: | Molecular cell biology and Immunology, CCA - Immuno-pathogenesis |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Stromal cell animal structures Angiogenesis Basic fibroblast growth factor Breast Neoplasms Biology Article Neovascularization chemistry.chemical_compound Twist transcription factor Mice Cell Line Tumor medicine Macrophage Animals Humans Chemokine CCL2 Tumor microenvironment Neovascularization Pathologic Macrophages Twist-Related Protein 1 Mammary Neoplasms Experimental Nuclear Proteins Oncology chemistry Tumor progression Cancer research Disease Progression Female medicine.symptom |
| Zdroj: | Low-Marchelli, J M, Ardi, V C, Vizcarra, E A, van Rooijen, N, Quigley, J P & Yang, J 2013, ' Twist1 Induces CCL2 and Recruits Macrophages to Promote Angiogenesis ', Cancer Research, vol. 73, no. 2, pp. 662-671 . https://doi.org/10.1158/0008-5472.CAN-12-0653 Cancer Research, 73(2), 662-671. American Association for Cancer Research Inc. |
| ISSN: | 0008-5472 |
| DOI: | 10.1158/0008-5472.CAN-12-0653 |
| Popis: | The transcription factor Twist1 induces epithelial–mesenchymal transition and extracellular matrix degradation to promote tumor metastasis. Although Twist1 also plays a role in embryonic vascular development and tumor angiogenesis, the molecular mechanisms that underlie these processes are not as well understood. Here, we report a novel function for Twist1 in modifying the tumor microenvironment to promote progression. We found that expression of Twist1 in human mammary epithelial cells potently promoted angiogenesis. Surprisingly, Twist1 expression did not increase the secretion of the common proangiogenic factors VEGF and basic fibroblast growth factor but rather induced expression of the macrophage chemoattractant CCL2. Attenuation of endogenous Twist1 in vivo blocked macrophage recruitment and angiogenesis, whereas exogenous CCL2 rescued the ability of tumor cells lacking Twist1 to attract macrophages and promote angiogenesis. Macrophage recruitment also was essential for the ability of Twist1-expressing cells to elicit a strong angiogenic response. Together, our findings show that how Twist1 recruits stromal macrophages through CCL2 induction to promote angiogenesis and tumor progression. As Twist1 expression has been associated with poor survival in many human cancers, this finding suggests that anti-CCL2 therapy may offer a rational strategy to treat Twist1-positive metastatic cancers. Cancer Res; 73(2); 662–71. ©2012 AACR. |
| Databáze: | OpenAIRE |
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