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Title: Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth
Authors: Pestell, Timothy G.
Jiao, Xuanmao
Kumar, Mukesh
Peck, Amy R.
Prisco, Marco
Deng, Shengqiong
Li, Zhiping
Ertel, Adam
Casimiro, Mathew C.
Ju, Xiaoming
Di Rocco, Agnese
Di Sante, Gabriele
Katiyar, Sanjay
Shupp, Alison
Lisanti, Michael P.
Jain, Pooja
Wu, Kongming
Rui, Hallgeir
Hooper, Douglas C.
Yu, Zuoren
Goldman, Aaron R.
Speicher, David W.
Laury-Kleintop, Lisa
Pestell, Richard G.
Keywords: OPN
Cyclin D1
Issue Date: 2017
Source: Pestell, T. G., Jiao, X., Kumar, M., Peck, A. R., Prisco, M., Deng, S., et al. (2017). Stromal cyclin D1 promotes heterotypic immune signaling and breast cancer growth. Oncotarget, 8(47), 81754-81775.
Series/Report no.: Oncotarget
Abstract: The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1Stroma) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy. Cyclin D1Stroma had profound effects on the breast tumor microenvironment increasing the recruitment of F4/80+ and CD11b+ macrophages and increasing angiogenesis. Cyclin D1Stroma induced secretion of factors that promoted expansion of stem cells (breast stem-like cells, embryonic stem cells and bone marrow derived stem cells). Cyclin D1Stroma resulted in increased secretion of proinflammatory cytokines (CCL2, CCL7, CCL11, CXCL1, CXCL5, CXCL9, CXCL12), CSF (CSF1, GM-CSF1) and osteopontin (OPN) (30-fold). OPN was induced by cyclin D1 in fibroblasts, breast epithelial cells and in the murine transgenic mammary gland and OPN was sufficient to induce stem cell expansion. These results demonstrate that cyclin D1Stroma drives tumor microenvironment heterocellular signaling, promoting several key hallmarks of cancer.
DOI: 10.18632/oncotarget.19953
Rights: © 2017 Pestell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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