%0 Journal Article
%T 3D culture reveals a signaling network
%A Senthil K Muthuswamy
%J Breast Cancer Research
%D 2011
%I BioMed Central
%R 10.1186/bcr2800
%X Some of us may remember conferences with sessions entitled 'Why 3D?' Such sessions are a thing of the past now because there is an accumulating body of evidence - joined by the recent article from Leslie and colleagues [1] - demonstrating the importance and utility of 3D culture systems to discover and model biological process with in vivo relevance. For example, when normal and malignant human breast cells are placed in 3D cultures of laminin-rich gels, the former cells form growth-arrested, lumen-containing acini and the latter cells form disorganized structures [2]. Inhibitors of epidermal growth factor receptor and ¦Â1-integrin can 'revert' the malignant phenotype, and each inhibitor downmodulates its own target as well as the other targets only in 3D but not in cells grown as monolayer cultures - suggesting that signaling pathways reciprocally regulate each other to maintain the transformed state [3]. ErbB2/HER2-induced transformation of 3D structures, but not cell proliferation, requires disruption of the Par6 cell polarity pathway [4]. This requirement for deregulation of cell polarity pathways is also observed during ErbB2-induced mammary tumorigenesis in mouse models of human breast cancer [5]. Cells in a 3D matrix can thus provide novel and unexpected insights into cancer biology.Leslie and colleagues demonstrate an unexpected role for the 3D context in regulating the ability of H-RasV12 to induce IL-6 and activate STAT3 [1]. Consistent with previous reports on the role played by STAT3 [6,7], the authors first demonstrate that downregulation of STAT3 inhibits the ability of H-RasV12 to transform MCF-10A cells. While there was no increase in tyrosine phosphorylation of STAT3 when H-RasV12-transformed MCF-10A cells were grown as monolayer cultures, the authors surprisingly observed a significant increase in phospho-STAT3 and IL-6, a potent activator of STAT3 phosphorylation in tumors derived from H-RasV12-transformed MCF-10A cells. In addition, spontaneous mo
%U http://breast-cancer-research.com/content/13/1/103