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Authors (citation) | Cancer cell lines used | Stromal cell lines used | Type of coculture | Special separation techniques | Linked to human in vivo data | Major findings |
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Rozenchan et al. (2009) [37] | MCF10A, MDA-MB-231 | Primary CAFs and NAFs | Transwell | No | No | Epithelial cell lines upregulate different pathways when cocultured with the two types of fibroblasts. MDA-MB-231-CAF cocultures (CAFs) upregulate β-catenin/TCF pathway genes; MDA-MB-231-NAF cocultures downregulate glycolipid and fatty acid biosynthesis. MCF10A-CAF cocultures upregulate stress response genes, while MCF10A-NAF cocultures downregulate growth control and adhesion genes. |
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Santos et al. (2011) [38] | MDA-MB-231, MDA-MB-435, MCF7 | Primary fibroblasts from positive and negative LN | Transwell | No | No | Gene expression changes induced by coculture with fibroblasts from positive and negative nodes are distinct and intrinsic to each tumor subtype. |
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Camp et al. (2010) [35] | MCF7, T47D, ZR75, Sum102, Sum149, HCC1537 | Immortalized reduction mammary fibroblasts | Direct physical contact and transwell | Yes | Computational deconvolution | The response to fibroblast coculture differs between basal-like and luminal cancer cell lines. The genes that distinguish basal-like versus luminal cultures also distinguishes human tumors. Basal-likes upregulate interleukins and chemokines (IL-6, IL-8, CXCL1, CXCL3, TGF-β) and TWIST and SOD1. Luminal cells increase stress response genes. |
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Buess et al. (2009) [39] | Hs578T, BT549, MDA-MB-436, MDA-MB-231, HMEC, SKBR-3, MCF7, T47D, HMECs | Stromal fibroblasts: human dermal fibroblasts, embryonic lung fibroblasts, and breasts fibroblasts | Direct physical contact & transwell | Yes | Computational deconvolution | Interaction between some breast cancer cells and stromal fibroblasts induced interferon response. The presence of this response is associated with higher risk of tumor progression. |
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Buess et al. (2009) [40] | HMECs, MCF7, T47D, MDA-MB-231, SKBR-3, Hs578T, BT549 | HuVECs and human dermal microvascular endothelial cells | Direct physical contact & transwell | Yes | Computational deconvolution | Induction of an “M-phase cell cycle genes” in breast cancer cell lines but not in normal epithelium. Tumors with this gene signature have increased metastasis and worse overall survival. Endothelial cells induce proliferation in CD44+/CD24− cancer cells. |
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Liu et al. (2011) [41] | Sum159, Sum149, MCF7 | Human bone marrow-derived mesenchymal cells | Direct physical contact and transwell | No | No | MSCs regulate cancer cell behavior through their effects on cancer stem cells. Networks of cytokines (IL-6, IL-8, CXCL1, CXCL5, and CXCL6 are associated with migration of cancer cells). |
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Wadlow et al. (2009) [42] | Many commercially available cancer cell lines | Many commercially available normal skin and lung fibroblasts | Direct physical contact | No | No | Cancer cell proliferation is modulated both by the cancer cell and the fibroblasts. Two functionally distinct pathways associated with altered proliferation were identified, one of which showed features of activated mesenchyme. |
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