Chemotaxis in cancer
TLDR
This Review summarizes how chemotaxis directs the different behaviours of tumour cells and stromal cells in vivo, how molecular pathways regulateChemotaxis in tumours and how chemtaxis choreographs cell behaviour to shape the tumour microenvironment and to determine metastatic spread.Abstract:
Chemotaxis of tumour cells and stromal cells in the surrounding microenvironment is an essential component of tumour dissemination during progression and metastasis. This Review summarizes how chemotaxis directs the different behaviours of tumour cells and stromal cells in vivo, how molecular pathways regulate chemotaxis in tumour cells and how chemotaxis choreographs cell behaviour to shape the tumour microenvironment and to determine metastatic spread. The central importance of chemotaxis in cancer progression is highlighted by discussion of the use of chemotaxis as a prognostic marker, a treatment end point and a target of therapeutic intervention.read more
Citations
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Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion.
TL;DR: The present study provides the evidence that the chemokine receptor C CR5 is highly expressed and associated with poor prognosis in human GBM and suggests that the CCR5 is a critical molecular event associated with gliomagenesis.
Impact of Dimensionality and Network Disruption on Microrheology of Cancer Cells in 3D Environments
TL;DR: The results demonstrate that metastatic breast cancer cells (MDA-MB-231) exhibit more solid-like internal motions in 3D compared to 2D, and actin network disruption via Cytochalasin D has a more pronounced effect on internal cell fluctuations in 2D.
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Study of the Chemotactic Response of Multicellular Spheroids in a Microfluidic Device
Jose M. Ayuso,Haneen A. Basheer,Rosa Monge,Pablo Sánchez-Álvarez,Manuel Doblaré,Steven D. Shnyder,Victoria Vinader,Kamyar Afarinkia,Luis J. Fernández,Ignacio Ochoa +9 more
TL;DR: It is observed that spheroids of oral squamous carcinoma cells OSC–19 invade collectively in the direction of the gradient of FBS, which is more directional and aggressive than that observed for individual cells in the same experimental setup.
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Inducing chemotactic and haptotactic cues in microfluidic devices for three-dimensional in vitro assays
TL;DR: 3D diffusion experiments are performed using microfluidic platforms in order to quantify the distribution of PDGF-BB and TGF-β1 across collagen and fibrin gels and are reproduced by computer simulations based on a reaction-diffusion transport model, confirming that diffusion and binding phenomena are established within the microdevice.
Journal ArticleDOI
Targeting Triple-Negative Breast Cancer with Combination Therapy of EGFR CAR T Cells and CDK7 Inhibition
Lin Xia,Zheng Zaozao,Jun-yi Liu,Yu-jie Chen,Jiancheng Ding,Guo-sheng Hu,Ya-hong Hu,Suling Liu,Wenxin Luo,Ningshao Xia,Wen Liu +10 more
Abstract: EGFR-targeted chimeric antigen receptor (CAR) T cells are potent and specific in suppressing the growth of triple-negative breast cancer (TNBC) in vitro and in vivo. However, in this study, a subset of mice soon acquired resistance, which limits the potential use of EGFR CAR T cells. We aimed to find a way to overcome the observed resistance. Transcriptomic analysis results revealed that EGFR CAR T-cell treatment induced a set of immunosuppressive genes, presumably through IFNγ signaling, in EGFR CAR T-cell-resistant TNBC tumors. The EGFR CAR T-cell-induced immunosuppressive genes were associated with EGFR CAR T-cell-activated enhancers and were especially sensitive to THZ1, a CDK7 inhibitor we screened out of a panel of small molecules targeting epigenetic modulators. Accordingly, combination therapy with THZ1 and EGFR CAR T cells suppressed immune resistance, tumor growth, and metastasis in TNBC tumor models, including human MDA-MB-231 cell-derived and TNBC patient-derived xenografts, and mouse EMT6 cell-derived allografts. Taken together, we demonstrated that transcriptional modulation using epigenetic inhibitors could overcome CAR T-cell therapy-induced immune resistance, thus providing a therapeutic avenue for treating TNBC in the clinic.
References
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Epithelial-Mesenchymal Transitions in Development and Disease
Jean Paul Thiery,Jean Paul Thiery,Hervé Acloque,Ruby Yun-Ju Huang,Ruby Yun-Ju Huang,M. Angela Nieto +5 more
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
Journal ArticleDOI
Myeloid-derived suppressor cells as regulators of the immune system.
TL;DR: The origin, mechanisms of expansion and suppressive functions of MDSCs, as well as the potential to target these cells for therapeutic benefit are discussed.
Journal ArticleDOI
Involvement of chemokine receptors in breast cancer metastasis.
Anja Müller,Bernhard Homey,Hortensia Soto,Nianfeng Ge,Daniel Catron,Matthew E. Buchanan,Terri McClanahan,Erin Murphy,Wei Yuan,Stephan N. Wagner,Jose Luis Barrera,Alejandro Mohar,Emma Verastegui,Albert Zlotnik +13 more
TL;DR: It is reported that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases and their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis.
Journal ArticleDOI
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Tyler J. Curiel,George Coukos,Linhua Zou,Xavier Alvarez,Pui Cheng,Peter Mottram,Melina Evdemon-Hogan,Jose R. Conejo-Garcia,Lin Zhang,Matthew E. Burow,Yun Zhu,Shuang Wei,Ilona Kryczek,Ben Daniel,Alan N. Gordon,Leann Myers,Andrew A. Lackner,Mary L. Disis,Keith L. Knutson,Lieping Chen,Weiping Zou +20 more
TL;DR: It is shown, in detailed studies of CD4+CD25+FOXP3+ Treg cells in 104 individuals affected with ovarian carcinoma, that human tumor T Reg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo.
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Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer
Massimo Cristofanilli,G. Thomas Budd,Matthew J. Ellis,Alison Stopeck,Jeri Matera,M. Craig Miller,James M. Reuben,Gerald V. Doyle,W. Jeffrey Allard,Leon W.M.M. Terstappen,Daniel F. Hayes +10 more
TL;DR: The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.
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