期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1830, 期 9, 页码 4314-4320出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2013.03.033
关键词
Fibronectin; Tumor angiogenesis; Integrins; Preadipocytes; Conducting polymers; Bioelectronics
资金
- National Cancer Institute [RC1CA146065, R21CA161532]
- American Brain Tumour Association
- National Science Foundation
- Partner University Fund (a program of French American Cultural Exchange)
- Cornell Center on the Microenvironment Metastasis [U54CA143876]
- Directorate For Engineering
- Div Of Civil, Mechanical, & Manufact Inn [1031139] Funding Source: National Science Foundation
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [0908994] Funding Source: National Science Foundation
Background: Changes in fibronectin (Fn) matrix remodeling contribute to mammary tumor angiogenesis and are related to altered behavior of adipogenic stromal cells; yet, the underlying mechanisms remain unclear due in part to a lack of reductionist model systems that allow the inherent complexity of cell-derived extracellular matrices (ECMs) to be deciphered. In particular, breast cancer-associated adipogenic stromal cells not only enhance the composition, quantity, and rigidity of deposited Fn, but also partially unfold these matrices. However, the specific effect of Fn conformation on tumor angiogenesis is undefined. Methods: Decellularized matrices and a conducting polymer device consisting of poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS) were used to examine the effect of Fn conformation on the behavior of 3T3-L1 preadipocytes. Changes in cell adhesion and proangiogenic capability were tested via cell counting and by quantification of vascular endothelial growth factor (VEGF) secretion, respectively. Integrin-blocking antibodies were utilized to examine varied integrin specificity as a potential mechanism. Results: Our findings suggest that tumor-associated partial unfolding of Fn decreases adhesion while enhancing VEGF secretion by breast cancer-associated adipogenic precursor cells, and that altered integrin specificity may underlie these changes. Conclusions and general significance: These results not only have important implications for our understanding of tumorigenesis, but also enhance knowledge of cell-ECM interactions that may be harnessed for other applications including advanced tissue engineering approaches. This article is part of a Special Issue entitled Organic Bioelectronics - Novel Applications in Biomedicine.
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