Metastasis: recent discoveries and novel treatment strategies

Eccles, Suzanne A.; Welch, Danny R.

doi:10.1016/s0140-6736(07)60781-8

Cited by 663 publications

(539 citation statements)

References 206 publications

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“…The foremost cause of death in cancer patients is not by the primary tumors, as they are usually surgically removed, but rather by the development of metastases and the recurrence of the disease (18,19). Interestingly, in many cancers, metastases are more likely to form only after the primary tumor is removed.…”

Section: Discussionmentioning

confidence: 99%

Recognition and Prevention of Tumor Metastasis by the NK Receptor NKp46/NCR1

Glasner¹,

Ghadially²,

Gur³

et al. 2012

The Journal of Immunology

147

119

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NK cells employ a variety of activating receptors to kill virally infected and tumor cells. Prominent among these receptors are the natural cytotoxicity receptors (NCRs) (NKp30, NKp44, and NKp46), of which only NKp46 has a mouse ortholog (NCR1). The tumor ligand(s) of NKp46/NCR1 is still unknown, but it was shown that the human NKp46 and the mouse NCR1 are involved in tumor eradication both in vitro and in vivo. Whether any of the NK activating receptors is involved in the prevention of tumor metastasis is unknown. To address this question, we studied the activity of the NK cell receptor NKp46/NCR1 in two spontaneous metastasis models, the B16F10.9 melanoma (B16) and the Lewis lung carcinoma (D122) in the NCR1 knockout mouse that was generated by our group, in various in vitro and in vivo assays. We demonstrated that all B16 and D122 tumors, including those generated in vivo, express an unknown ligand(s) for NKp46/NCR1. We have characterized the properties of the NKp46/NCR1 ligand(s) and demonstrated that NKp46/NCR1 is directly involved in the killing of B16 and D122 cells. Importantly, we showed in vivo that NKp46/NCR1 plays an important role in controlling B16 and D122 metastasis. Thus, to our knowledge, in this study we provide the first evidence for the direct involvement of a specific NK killer receptor in preventing tumor metastasis.

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Section: Discussionmentioning

confidence: 99%

Recognition and Prevention of Tumor Metastasis by the NK Receptor NKp46/NCR1

Glasner¹,

Ghadially²,

Gur³

et al. 2012

The Journal of Immunology

147

119

View full text Add to dashboard Cite

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“…This event occurs mainly through intravasation of lymphatic and blood vessels, although some cancer cells are also able to spread through interstitial tissues under the basal lamina or directly into the peritoneal cavity (e.g., ovarian carcinoma). The metastatic process involves a succession of cellular events comprising tumor angiogenesis, acquisition of an invasive phenotype by primary tumor cells, intravasation of cancer cells into blood and lymphatic vessels, attachment to a target organ, and establishment of a secondary tumor [72][73][74][75]. In this complex succession of events, the phenotypical change of tumor cells to acquire invasive abilities is absolutely necessary.…”

Section: Purinergic Signaling Emt and Invasivenessmentioning

confidence: 99%

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Martinez-Ramirez

Dı́az-Muñoz

Butanda-Ochoa

et al. 2016

Purinergic Signalling

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The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.Keywords P2 receptors . P1 receptors . Purinergic signaling . Cell migration . EMTThe purinergic system of intercellular communication General aspects The term purine (from: pure urine) was created more than 130 years ago by Emil Fischer after detailed analytical characterization of the uric acid molecule [1]. Purine molecular structure is the result of fusing pyrimidine and imidazole rings, and it exists as four N-H tautomeric forms [2]. Tautomerism of purine bases in DNA is one of the earliest reasons for mutations [3][4][5]. The interconversion of the different adenine or guanine tautomers produced mispairing with pyrimidines (which also show tautomeric forms) that may lead to changes in DNA sequence [6].Purine molecules appeared very early in the history of our planet, in the period known as Borganic evolution^, before the establishment of living systems. It has been postulated that purines could be formed by a eutectic (denoting a mixture of substances in fixed proportions that melts and freezes at a single temperature that is lower than the melting points of any of the separate constituents) concentration of HCN at extremely low temperature over a period of dozens of years [7]. Purine molecules, such as adenine and guanine, are components of the genetic material (DNA and RNA) of all living beings. Purine and pyrimidine tautomeric equilibria in nucleic acids was postulated to be significant in events such as DNA replication and repair as well as in the occurrence of point mutations [8].As nucleosides and nucleotides, purines play other highly strategic roles, acting as energy intermediates, allosteric regulators of key metabolic activities, redox molecules, and chemical messengers for signal transduction events. The two most important purines serving as extracellular ligands for paracrine and autocrine signaling are ATP and its dephosphorylated form, adenosine (ADO). ATP and ADO act as intracellular intermediate metabolites, and their presence in the

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“…Type IV collagen increases tumor cell resistance to anoikis The ECM provides survival signals to the cells and has been linked to the ability of tumor cells to evade cell detachment-induced apoptosis (anoikis) and metastasize (Eccles and Welch, 2007;Decker et al, 2008;Simpson et al, 2008). Liver metastasis, in particular, was shown to be associated with an increased cell capacity to resist anoikis (Duxbury et al, 2004).…”

Section: Col3a1mentioning

confidence: 99%

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

et al. 2011

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The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27 IGFÀIR murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen a1 and a2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/a2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by smallinterfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases.

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Metastasis: recent discoveries and novel treatment strategies

Cited by 663 publications

References 206 publications

Recognition and Prevention of Tumor Metastasis by the NK Receptor NKp46/NCR1

Recognition and Prevention of Tumor Metastasis by the NK Receptor NKp46/NCR1

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Type IV collagen-initiated signals provide survival and growth cues required for liver metastasis

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