Journal ArticleDOI
SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion
Takanori Kitamura,Kohei Kometani,Hiroki Hashida,Akihiro Matsunaga,Hiroyuki Miyoshi,Hisahiro Hosogi,Masahiro Aoki,Masanobu Oshima,Masanobu Oshima,Masakazu Hattori,Arimichi Takabayashi,Nagahiro Minato,Makoto Mark Taketo +12 more
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TLDR
It is shown that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front and accumulation of iMCs that promote tumor invasion in cis-Apc/Smad4 mice.Abstract:
Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion.read more
Citations
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Immunity, Inflammation, and Cancer
TL;DR: The principal mechanisms that govern the effects of inflammation and immunity on tumor development are outlined and attractive new targets for cancer therapy and prevention are discussed.
Journal ArticleDOI
Macrophage Diversity Enhances Tumor Progression and Metastasis
Bin-Zhi Qian,Jeffrey W. Pollard +1 more
TL;DR: There is persuasive clinical and experimental evidence that macrophages promote cancer initiation and malignant progression, and specialized subpopulations of macrophage may represent important new therapeutic targets.
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Microenvironmental regulation of metastasis
TL;DR: Experimental data demonstrating the role of the microenvironment in metastasis is described, areas for future research are identified and possible new therapeutic avenues are suggested.
Journal ArticleDOI
Tumor-associated macrophages: from mechanisms to therapy.
TL;DR: Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment.
Journal ArticleDOI
Inflammation and Colon Cancer
TL;DR: The role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis, are elucidated.
References
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Journal ArticleDOI
Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
Journal ArticleDOI
Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion
Akira Orimo,Piyush Gupta,Dennis C. Sgroi,Fernando Arenzana-Seisdedos,Thierry Delaunay,Rizwan Naeem,Vincent J. Carey,Andrea L. Richardson,Robert A. Weinberg +8 more
TL;DR: Using a coimplantation tumor xenograft model, it is demonstrated that carcinoma-associated fibroblasts extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammaries derived from the same patients.
Journal ArticleDOI
Tumour-educated macrophages promote tumour progression and metastasis
TL;DR: Macrophages are educated by the tumour microenvironment, so that they adopt a trophic role that facilitates angiogenesis, matrix breakdown and tumour-cell motility — all of which are elements of the metastatic process.
Journal ArticleDOI
Tumour-cell invasion and migration: diversity and escape mechanisms
Peter Friedl,Katarina Wolf +1 more
TL;DR: Cancer cells possess a broad spectrum of migration and invasion mechanisms and learning more about the cellular and molecular basis of these different migration/invasion programmes will help to understand how cancer cells disseminate and lead to new treatment strategies.
Journal ArticleDOI
VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
Rosandra N. Kaplan,Rebecca D. Riba,Stergios Zacharoulis,Anna H. Bramley,Loic Vincent,Carla Costa,Daniel D. MacDonald,David K. Jin,Koji Shido,Scott A. Kerns,Zhenping Zhu,Daniel J. Hicklin,Yan Wu,Jeffrey L. Port,Nasser K. Altorki,Elisa Port,Davide Ruggero,Sergey V. Shmelkov,Kristian K. Jensen,Shahin Rafii,David Lyden +20 more
TL;DR: A requirement for VEGFR1+ haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells is demonstrated.
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VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
Rosandra N. Kaplan,Rebecca D. Riba,Stergios Zacharoulis,Anna H. Bramley,Loic Vincent,Carla Costa,Daniel D. MacDonald,David K. Jin,Koji Shido,Scott A. Kerns,Zhenping Zhu,Daniel J. Hicklin,Yan Wu,Jeffrey L. Port,Nasser K. Altorki,Elisa Port,Davide Ruggero,Sergey V. Shmelkov,Kristian K. Jensen,Shahin Rafii,David Lyden +20 more