Cancer Tills the Premetastatic Field: Mechanistic Basis and Clinical Implications

Chin, Andrew R.; Wang, Shizhen Emily

doi:10.1158/1078-0432.ccr-16-0028

Cited by 97 publications

(71 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The contribution of lymphatic flow to tumor immune evasion is supported by the evidence that a permissive environment is created in tumor-draining lymph nodes, the so-called “metastatic niche” [reviewed elsewhere (195)]. The presence of tumor cells in the sentinel lymph node, that is, the first lymph node draining the region of the tumor, is associated with disease progression and often changes clinical management.…”

Section: Role Of Lecs In Immune Suppression and Tolerancementioning

confidence: 99%

The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment

et al. 2016

View full text Add to dashboard Cite

Recently developed cancer immunotherapy approaches including immune checkpoint inhibitors and chimeric antigen receptor T cell transfer are showing promising results both in trials and in clinical practice. These approaches reflect increasing recognition of the crucial role of the tumor microenvironment in cancer development and progression. Cancer cells do not act alone, but develop a complex relationship with the environment in which they reside. The host immune response to tumors is critical to the success of immunotherapy; however, the determinants of this response are incompletely understood. The immune cell infiltrate in tumors varies widely in density, composition, and clinical significance. The tumor vasculature is a key component of the microenvironment that can influence tumor behavior and treatment response and can be targeted through the use of antiangiogenic drugs. Blood vascular and lymphatic endothelial cells have important roles in the trafficking of immune cells, controlling the microenvironment, and modulating the immune response. Improving access to the tumor through vascular alteration with antiangiogenic drugs may prove an effective combinatorial strategy with immunotherapy approaches and might be applicable to many tumor types. In this review, we briefly discuss the host’s immune response to cancer and the treatment strategies utilizing this response, before focusing on the pathological features of tumor blood and lymphatic vessels and the contribution these might make to tumor immune evasion.

show abstract

Section: Role Of Lecs In Immune Suppression and Tolerancementioning

confidence: 99%

The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Consequently, VEGF receptor (VEGFR) 1-positive bone marrowderived hematopoietic progenitor cells are recruited and the ECM is modulated at these sites. This already 'primed' tissue, which does not yet harbor tumor cells, provides the 'soil' for future metastasis and is called the premetastatic niche [21][22][23].…”

Section: Micrometastasis Formationmentioning

confidence: 99%

Underlying Mechanisms for Distant Metastasis - Molecular Biology

2017

View full text Add to dashboard Cite

Concepts of MetastasisIn 1889, the English surgeon Stephen Paget illustrated his theory on metastasis with the sentence 'When a plant goes to seed, its seeds are carried in all directions, but they can only live and grow if they fall on congenial soil'. He based this 'seed and soil' hypothesis on autopsy records where he detected a discrepancy between the blood supply and frequency of metastasis in specific organs. He concluded that the development of metastasis depends on distinctive features of the tumor cells as well as the specific target organs [1,2]. This concept replaced the mechanistic hypothesis of Rudolf Virchow who considered metastasis as the arrest of tumor cell emboli in the vasculature [2]. Nowadays, metastasis is understood as a complex process of molecular and biochemical events performed by multiple actors. The concept of a 'homogenous seed' has been replaced by a heterogeneous hierarchically organized system of tumorigenic cancer stem cells and their non-tumorigenic progeny [3]. Cancer stem cells are now regarded to be the major driver in metastasis development. In addition, the idea of a sequential development of a cancer from a single primary tumor to the subsequent spread to distant sites was abandoned in the last years and replaced by a model of a simultaneous progression towards metastatic tumor disease. The currently favored model describes the evolution of systemic tumor disease as a parallel development of primary tumor and distant metastasis caused by heterogeneous tumor subpopulations [4].To understand the cellular and molecular basis of metastasis, the most acknowledged approach is the concept of the invasionmetastasis cascade proposed by Isaiah J. Fidler in 2003 and subsequently adapted by Scott Valastyan in 2011 [5,6]. The authors distinguish 6 steps in the process from primary local tumor to distant Keywords Metastasis · Molecular mechanism · Cancer therapy Summary Background:The formation of distant metastases constitutes a complex process with a variety of different genes and pathways involved. To improve patient survival, it is necessary to understand the underlying mechanisms of metastasis to allow for targeted intervention. Methods: This review provides an overview of the general concepts of metastasis, focusing on the most important genes and pathways involved and on interventional strategies. Results: Cancer cells undergo different steps to form metastasis: most prominently, local invasion, intravasation, survival in the circulation, arrest at a distant organ site and extravasation, micrometastasis formation, and metastatic colonization. In order to pass these steps, different molecular pathways are of major importance: EGF/RAS/ RAF/MEK/ERK, PI3K/Akt/mTOR, HGF/Met, Wnt/ -catenin, and VEGF signaling. The HGF/Met regulator MACC1 and the Wnt signaling target S100A4 have been shown to play a major role in the metastatic process. Each gene and pathway provides an opportunity for therapeutic intervention. Conclusion: Since metastasis represents a highly limiting factor in cancer...

show abstract

“…Starting from the "seed and soil" hypothesis, postulated by Paget, up to date, it is well known that cancer cells (the seed) require a specific and compatible "soil" microenvironment, the pre-metastatic niche, which is able to evolve and to promote both cell engraftment, creating the metastatic niche, and cell proliferation, leading to the micro-to macro-metastatic transition [114][115][116][117][118][119] . Many evidences demonstrate how primary tumor site is able to modify, before cancer cells' arrival, the secondary organ microenvironment, stimulating the creation of the pre-metastatic niche [120] .…”

Section: Metastatic Nichementioning

confidence: 99%

Circulating tumor cells and the metastatic process: the complexity of malignancy

Raimo¹,

Santis²,

Coppola³

et al. 2018

JCMT

View full text Add to dashboard Cite

Despite improvements achieved in terms of early detection and therapeutic approach, metastatic breast cancer remains one of the principal worldwide causes of death. In recent years, due to the heterogeneous response of each patient to chemotherapy, clinical research highlights the need of a personalized approach. Circulating tumor cells (CTCs) represents a promising tool for this purpose. Unfortunately, even if their correlation with severity, outcome and metastatic nature of the tumor has been established, several issues, mainly concerning their characterization and isolation, need to be solved. In this review, latest knowledge on CTCs and metastatic process in breast cancer were analyzed, aiming to understand their clinical utility and validity for a prospective therapeutic scenario.

show abstract

Cancer Tills the Premetastatic Field: Mechanistic Basis and Clinical Implications

Cited by 97 publications

References 99 publications

The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment

The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment

Underlying Mechanisms for Distant Metastasis - Molecular Biology

Circulating tumor cells and the metastatic process: the complexity of malignancy

Contact Info

Product

Resources

About