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Journal ArticleDOI

Contribution of platelets to tumour metastasis.

01 Feb 2011-Nature Reviews Cancer (Nature Publishing Group)-Vol. 11, Iss: 2, pp 123-134
TL;DR: Contributions of platelets to tumour cell survival and spread suggest platelets as a new avenue for therapy.
Abstract: Experimental evidence suggests that platelets contribute to metastasis through adhesive and haemostatic functions that promote cancer cell survival, immune evasion and interactions with vascular cells to assist organ colonization from the bloodstream. Extensive experimental evidence shows that platelets support tumour metastasis. The activation of platelets and the coagulation system have a crucial role in the progression of cancer. Within the circulatory system, platelets guard tumour cells from immune elimination and promote their arrest at the endothelium, supporting the establishment of secondary lesions. These contributions of platelets to tumour cell survival and spread suggest platelets as a new avenue for therapy.
Citations
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Journal ArticleDOI
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Abstract: Cancers develop in complex tissue environments, which they depend on for sustained growth, invasion and metastasis. Unlike tumor cells, stromal cell types within the tumor microenvironment (TME) are genetically stable and thus represent an attractive therapeutic target with reduced risk of resistance and tumor recurrence. However, specifically disrupting the pro-tumorigenic TME is a challenging undertaking, as the TME has diverse capacities to induce both beneficial and adverse consequences for tumorigenesis. Furthermore, many studies have shown that the microenvironment is capable of normalizing tumor cells, suggesting that re-education of stromal cells, rather than targeted ablation per se, may be an effective strategy for treating cancer. Here we discuss the paradoxical roles of the TME during specific stages of cancer progression and metastasis, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.

5,396 citations

Journal ArticleDOI
09 Feb 2017-Cell
TL;DR: The cellular and molecular mechanisms involved in metastasis are summarized, with a focus on carcinomas where the most is known, and the general principles of metastasis that have begun to emerge are highlighted.

1,930 citations


Cites background from "Contribution of platelets to tumour..."

  • ...…when studies revealed that experimental induction of thrombocytopenia can exert an anti-metastatic effect (Gasic et al., 1968), while a high platelet count has for years been known to be associated with a poor clinical prognosis across diverse types of carcinomas (Gay and Felding-Habermann, 2011)....

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  • ...674 Cell 168, February 9, 2017 disseminated intravascular coagulation, and even large pulmonary emboli (Gay and Felding-Habermann, 2011)....

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  • ...Platelets contain a plethora of bioactive molecules that can potentially impact cancer progression and work in more recent years has revealed a number of mechanisms by which platelets can alter the fate of carcinoma cells in transit (Franco et al., 2015; Gay and Felding-Habermann, 2011)....

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  • ...…the normal homeostatic controls on coagulation, which can result in certain clotting symptoms that are seen in patients with cancer, specifically microthrombi, 674 Cell 168, February 9, 2017 disseminated intravascular coagulation, and even large pulmonary emboli (Gay and Felding-Habermann, 2011)....

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  • ..., 1968), while a high platelet count has for years been known to be associated with a poor clinical prognosis across diverse types of carcinomas (Gay and Felding-Habermann, 2011)....

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Journal ArticleDOI
TL;DR: It is shown that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis and inhibit NF-κB signaling in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo.

1,367 citations


Cites background from "Contribution of platelets to tumour..."

  • ...…lysis (Nieswandt et al., 1999; Palumbo et al., 2005), limits their exposure to shear stress, and promotes their adhesion to the endothelium (Erpenbeck and Schön, 2010; Gay and Felding-Habermann, 2011; Im et al., 2004; Jain et al., 2007; Karpatkin et al., 1988; Sierko andWojtukiewicz, 2007)....

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  • ..., 2005), limits their exposure to shear stress, and promotes their adhesion to the endothelium (Erpenbeck and Schön, 2010; Gay and Felding-Habermann, 2011; Im et al., 2004; Jain et al., 2007; Karpatkin et al., 1988; Sierko andWojtukiewicz, 2007)....

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Journal ArticleDOI
TL;DR: This Review summarizes the main processes and new mechanisms involved in the formation of the pre-metastatic niche and describes the main mechanisms used to modify organs of future metastasis.
Abstract: It is well established that organs of future metastasis are not passive receivers of circulating tumour cells, but are instead selectively and actively modified by the primary tumour before metastatic spread has even occurred. Sowing the 'seeds' of metastasis requires the action of tumour-secreted factors and tumour-shed extracellular vesicles that enable the 'soil' at distant metastatic sites to encourage the outgrowth of incoming cancer cells. In this Review, we summarize the main processes and new mechanisms involved in the formation of the pre-metastatic niche.

1,134 citations

Journal ArticleDOI
TL;DR: The metastatic process is reconstructed and the importance of key physical and mechanical processes at each step of the cascade is described, which may help to solve some long-standing questions in disease progression and lead to new approaches to developing cancer diagnostics and therapies.
Abstract: Metastasis is a complex, multistep process responsible for >90% of cancer-related deaths. In addition to genetic and external environmental factors, the physical interactions of cancer cells with their microenvironment, as well as their modulation by mechanical forces, are key determinants of the metastatic process. We reconstruct the metastatic process and describe the importance of key physical and mechanical processes at each step of the cascade. The emerging insight into these physical interactions may help to solve some long-standing questions in disease progression and may lead to new approaches to developing cancer diagnostics and therapies.

1,073 citations

References
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Journal ArticleDOI
TL;DR: This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in 2016 and is likely to be accompanied by neovascularization.
Abstract: THE growth of solid neoplasms is always accompanied by neovascularization. This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in f...

9,874 citations


Additional excerpts

  • ...Angiogenesis was originally hypothesized by Judah Folkma...

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Journal ArticleDOI
17 Nov 2006-Cell
TL;DR: Understanding of the origins and nature of cancer metastasis and the selection of traits that are advantageous to cancer cells is promoted.

3,863 citations

Journal ArticleDOI
TL;DR: Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy and could help to improve the treatment of metastatic disease.
Abstract: Metastases, rather than primary tumours, are responsible for most cancer deaths. To prevent these deaths, improved ways to treat metastatic disease are needed. Blood flow and other mechanical factors influence the delivery of cancer cells to specific organs, whereas molecular interactions between the cancer cells and the new organ influence the probability that the cells will grow there. Inhibition of the growth of metastases in secondary sites offers a promising approach for cancer therapy.

3,810 citations

Journal ArticleDOI
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.
Abstract: Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves rate-limiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.

3,332 citations


"Contribution of platelets to tumour..." refers background in this paper

  • ...Cells within the bloodstream that contribute to metastasis are endothelial cells, platelets, lymphocytes, macrophages, mast cells, fibroblasts and bone marrow-derived progenitor cell...

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Journal ArticleDOI
TL;DR: Clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.
Abstract: The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

2,894 citations