Premetastatic niche formation in the liver: emerging mechanisms and mouse models

Krüger, Achim

doi:10.1007/s00109-015-1342-7

Cited by 23 publications

(17 citation statements)

References 64 publications

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“…Liver metastasis formation is enhanced by angiogenesis‐stimulating factors, including TGF‐β1, VEGF‐A, and SDF‐1 . Transforming growth factor‐β1 plays important roles in embryonic development, cell proliferation, differentiation, angiogenesis, and wound healing . Furthermore, it is well known to be an immune and inflammation regulator.…”

Section: Discussionmentioning

confidence: 99%

“…(4,5) Transforming growth factor-b1 plays important roles in embryonic development, cell proliferation, differentiation, angiogenesis, and wound healing. (35,36) Furthermore, it is well known to be an immune and inflammation regulator. Upregulation of TGF-b1 induces EMT, a key step in processing metastasis formation, and this creates a microenvironment conducive to infiltration of the target organ by cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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Angiotensin II subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation

et al. 2017

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Liver metastases from colorectal cancer (CRC) are a clinically significant problem. The renin–angiotensin system is involved in tumor growth and metastases. This study was designed to evaluate the role of angiotensin II subtype receptor 1a (AT1a) in the formation of liver metastasis in CRC. A model of liver metastasis was developed by intrasplenic injection of mouse colon cancer (CMT‐93) into AT1a knockout mice (AT1aKO) and wild‐type (C57BL/6) mice (WT). Compared with WT mice, the liver weight and liver metastatic rate were significantly lower in AT1aKO. The mRNA levels of CD31, transforming growth factor‐ β1 (TGF‐β1), and F4/80 were suppressed in AT1aKO compared with WT. Double immunofluorescence analysis showed that the number of accumulated F4/80+ cells expressing TGF‐β1 in metastatic areas was higher in WT than in AT1aKO. The AT1aKO bone marrow (BM) (AT1aKO‐BM)→WT showed suppressed formation of liver metastasis compared with WT‐BM→WT. However, the formation of metastasis was further suppressed in WT‐BM→AT1aKO compared with AT1aKO‐BM→WT. In addition, accumulated F4/80+ cells in the liver metastasis were not BM‐derived F4/80+ cells, but mainly resident hepatic F4/80+ cells, and these resident hepatic F4/80+ cells were positive for TGF‐β1. Angiotensin II enhanced TGF‐β1 expression in Kupffer cells. Treatment of WT with clodronate liposomes suppressed liver metastasis by diminishing TGF‐β1+F4/80+ cells accumulation. The formation of liver metastasis correlated with collagen deposition in the metastatic area, which was dependent on AT1a signaling. These results suggested that resident hepatic macrophages induced liver metastasis formation by induction of TGF‐β1 through AT1a signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Angiotensin II subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation

et al. 2017

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“…For example, in both murine and human PDAC, the metastatic liver has been shown to exhibit significant alterations in its microarchitecture that are evident even with isolated tumor cells [70, 76]; these include the deposition of various ECM proteins (such as HA, collagen I and fibronectin), and activation of myofibroblast-like cells, as well as infiltrating immune cells [70, 76]. These changes are remarkable in that they have been shown to promote the engraftment of pancreatic cancer cells in mouse models and thus, constitute a defining characteristic of the hepatic premetastatic niche [77, 78]. Successful treatment of liver metastases in mice leads to regression of metastasis-associated ECM changes, attesting to the addiction of pancreatic cancer cells to desmoplasia [76].…”

Section: Cancer-associated Fibrosismentioning

confidence: 99%

Cancer Manipulation of Host Physiology: Lessons from Pancreatic Cancer

Zambirinis

Miller

2017

Trends in Molecular Medicine

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Homeostasis is a fundamental property of living organisms enabling the human body to withstand internal and external insults. In several chronic diseases, and especially in cancer, many homeostatic mechanisms are deranged. Pancreatic cancer, in particular, is notorious for its ability to invoke an intense fibro-inflammatory stromal reaction facilitating its progression and resistance to treatment. In the past decade, a number of seminal discoveries have elucidated previously unrecognized modes of commandeering the host’s defense systems. Here, we review novel discoveries in pancreatic cancer immunobiology and attempt to integrate the notion of deranged homeostasis in the pathogenesis of this disease. We also highlight areas of controversy and obstacles that need to be overcome, hoping to further our mechanistic insight into this malignancy.

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“…For the brain and bone, it is clear that much work remains to be done to determine whether premetastatic conditioning is relevant at these sites, and if so, what form it takes and how it is regulated [10,11]. Several features appear to be common between metastatic niches in different organs, in particular the creation of an immunosuppressive microenvironment appears essential for effective metastatic niche function in organs such as the lung, liver, and lymph node [6,12,13]. Nevertheless, clear differences between metastatic niches in different organs are also apparent.…”

mentioning

confidence: 99%

“…For example, due to its role in immunity, pre-metastatic changes in the lymph node counter-intuitively often initially restrict metastatic growth [6]. Cells unique to the liver such as hepatic sinusoidal endothelial cells, hepatocytes, and hepatic stellate cells make a major contribution to the microenvironmental support of metastatic outgrowth in the liver [12]. The osteoblastic niche can provide a ready-made metastatic niche for tumor cells that disseminate to the bone [11].…”

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confidence: 99%

Pre-metastatic conditioning of organ microenvironments by tumors: beyond preparing the soil

Sleeman

2015

J Mol Med

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Paget's Bseed and soil^hypothesis to explain patterns of cancer metastasis [1] must rank as the longest-enduring and most influential concept in oncology. Nevertheless, our understanding of what defines a metastatic Bseed^as well as the underlying cell and molecular basis of what constitutes a receptive microenvironmental Bsoil^is clearly only partial and continues to evolve to this day. For example, ideas about hierarchical tumor cell subpopulations founded on cancer stem cells clearly have important implications about whether all or only some tumor cells can act as seeds during metastasis formation [2].With regard to the soil in which metastases develop, recent years have witnessed rapid progress, and it is now clear that the nature of the soil is dynamic and can be influenced by a number of factors, including the primary tumor itself. In particular, seminal work from David Lyden's laboratory 10 years ago [3] has stimulated intensive work into defining what constitutes a metastatic niche-an organ microenvironment that supports the survival and outgrowth of disseminated tumor cells-and how factors released by tumors can condition organ microenvironments to create pre-metastatic niches in advance of tumor cell dissemination.The notion that tumor-derived factors can stimulate metastasis formation harks back to early ideas about how cancer dissemination occurs. Prior to the acceptance of cell theory as the basis of life and its application to pathology, various theories postulated that cancer was spread by poisonous or infectious Bjuices^pro-duced by tumors that caused transformation at secondary sites, leading to metastasis formation [4]. While metastasis is clearly not caused by secondary transformation but rather by dissemination of tumor cells from the primary cancer, nevertheless, it has emerged that factors that are shed and secreted by primary tumors can be decisive in metastasis formation through conditioning organ microenvironments in which metastases ultimately develop. Understanding these tumor-derived juices and the critical components within them is thus clearly an additional important aspect to be considered alongside the seed and soil and is obviously highly relevant therapeutically.Pre-metastatic conditioning likely contributes to a number of observations regarding metastasis formation. The concentration of factors produced by tumors that can induce a pre-metastatic niche in future sites of metastasis must presumably exceed a given threshold in order to condition the target organ microenvironment. This presumably contributes to the fact that the size of a primary tumor often correlates with the risk of metastasis formation [5]. Furthermore, as tumor-draining lymph nodes are exposed to high concentrations of metastatic niche-conditioning factors that are present in the lymphatic fluid they receive from the primary tumor, this must contribute at least in part to the prevalence of lymph node metastases for many types of cancer [6]. Moreover, some tumors such as melanoma metastasize while the primary t...

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Premetastatic niche formation in the liver: emerging mechanisms and mouse models

Cited by 23 publications

References 64 publications

Angiotensin II subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation

Angiotensin II subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation

Cancer Manipulation of Host Physiology: Lessons from Pancreatic Cancer

Pre-metastatic conditioning of organ microenvironments by tumors: beyond preparing the soil

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