Alteration of Cellular Behavior and Response to PI3K Pathway Inhibition by Culture in 3D Collagen Gels

Autor: Brian Fallica, Muhammad H. Zaman, Shaun Villa, Guy Makin, Joseph S. Maffei
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Integrins
Polyphosphoinositide Signaling Cascade
Pyridines
Cell Culture Techniques
lcsh:Medicine
Apoptosis
Extracellular matrix
Tissue culture
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Cell Movement
Neoplasms
Molecular Cell Biology
Basic Cancer Research
Signaling in Cellular Processes
lcsh:Science
0303 health sciences
Multidisciplinary
Microscopy
Confocal
Microscopy
Video
TOR Serine-Threonine Kinases
Signaling in Selected Disciplines
Signaling Cascades
Cell biology
Extracellular Matrix
Oncology
030220 oncology & carcinogenesis
MCF-7 Cells
Medicine
Signal transduction
Research Article
Signal Transduction
Blotting
Western
Phosphoinositide Signal Transduction
Biology
Signaling Pathways
Cell Growth
Collagen Type I
03 medical and health sciences
Cell Line
Tumor
Akt Signaling Cascade
Cell Adhesion
Humans
Cell adhesion
Furans
PI3K/AKT/mTOR pathway
030304 developmental biology
Cell Proliferation
Oncogenic Signaling
Cell growth
lcsh:R
Pyrimidines
Cell culture
Cancer cell
lcsh:Q
Tor Signaling
Gels
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 10, p e48024 (2012)
ISSN: 1932-6203
Popis: Most investigations into cancer cell drug response are performed with cells cultured on flat (2D) tissue culture plastic. Emerging research has shown that the presence of a three-dimensional (3D) extracellular matrix (ECM) is critical for normal cell behavior including migration, adhesion, signaling, proliferation and apoptosis. In this study we investigate differences between cancer cell signaling in 2D culture and a 3D ECM, employing real-time, live cell tracking to directly observe U2OS human osteosarcoma and MCF7 human breast cancer cells embedded in type 1 collagen gels. The activation of the important PI3K signaling pathway under these different growth conditions is studied, and the response to inhibition of both PI3K and mTOR with PI103 investigated. Cells grown in 3D gels show reduced proliferation and migration as well as reduced PI3K pathway activation when compared to cells grown in 2D. Our results quantitatively demonstrate that a collagen ECM can protect U2OS cells from PI103. Overall, our data suggests that 3D gels may provide a better medium for investigation of anti-cancer drugs than 2D monolayers, therefore allowing better understanding of cellular response and behavior in native like environments.
Databáze: OpenAIRE
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