Analysis of the lodgement and extravasation of tumor cells in experimental models of hematogenous metastasis

Kawaguchi, Takanori; Nakamura, K

doi:10.1007/bf00046424

Cited by 30 publications

(20 citation statements)

References 42 publications

(33 reference statements)

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“…After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10).…”

mentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

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Abstract. Exosomes are important contributors to cellMetastases are responsible for the death of a large majority of cancer patients despite considerable progress in surgical techniques, radiotherapy, chemotherapy and targeted therapies including immuno-therapy (1). A dramatic reduction of metastatic burden has been observed, however, tumor elimination is almost always incomplete. This phenomenon is based on drug resistance, which is due to adaptation of intracellular pathways or on activation of survival-supporting autocrine and paracrine pathways and several secreted factors expressed by drug-sensitive tumor cells after therapy (2). Metastasis can occur through release of cancer cells from the primary tumor into body cavities that holds true for ovarian and CNS tumors, or via hematogeneous and lymphatic vessels of the circulatory system (3). Metastases of some tumors are directed besides to lymph nodes to mainly one type of organ only, such as prostate cancer to the bones, pancreatic cancer and uveal melanoma to the liver, whereas tumors such as melanoma, breast-and lung cancer can colonize several types of organs (3). Tumor cells have been found in the blood of patients with early-stage cancer and in some cases even before the primary tumor has been diagnosed (4, 5). Recently, making use of single-cell expression profiling, it has been shown that early metastatic cells possess a stem-like gene signature and give rise to heterogeneous metastases (6). The metastatic process is characterized by a defined sequence of events (7,8). Initial steps are detachment from the extracellular matrix (ECM), invasion into the surrounding tissue and proteolysis of the basement membrane. After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10). After extravasation, colonization and outgrowth in the parenchyma of distant organs are the following steps. A common theme of the metastatic process is settlement of disseminated tumor cells (DTCs) into latency (dormancy), which can last from several months to decades (11). It has been observed that DTCs are recruited into pre-metastatic niches that support their survival by interactions with endothelial, myeloid cells, fibroblasts and other types of cells. After adaptation to the host microenvironment and suppression of an anti-tumoral immune response, DTCs are activated by not yet completely resolved mechanisms. Finally their outgrowth is based on an angiogenic switch mediated by pro-angiogenic factors and establishment of a vascular network to support the metabolic demands of colonizing tumor cells (12). In the follo...

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mentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

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“…Following the arrest and attachment of tumor cells to endothelial cells, platelets rapidly associate with the arrested tumor cell [27][28][29], leading to the induction of endothelial cell retraction [30], spreading of tumor cells on the subendothelial matrix, release of proteases and finally cell migration through the subendothelial matrix [27,28]. Platelets are capable of synthesizing TxA 2 but not prostacyclin (PGI 2 ).…”

Section: Discussionmentioning

confidence: 99%

Indomethacin Inhibits the Accumulation of Tumor Cells in Mouse Lungs and Subsequent Growth of Lung Metastases

Levin¹,

Kariv

Khomiak³

et al. 2000

Chemotherapy

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Background: The interaction of cancer cells with blood cells and cell wall components evokes inflammatory responses and is a critical event in the metastatic process. Indomethacin is a potent inhibitor of the cyclooxygenase (COX) enzymes and has previously been shown to decrease the growth of primary tumors in vivo. Proinflammatory prostaglandins produced by the two COX enzymes may also play a role in the development of metastases. Methods: To directly address this question, we tested the effect of indomethacin on the accumulation of circulating [³H]-uridine-labeled tumor cells in the lungs and on the subsequent development of lung tumors. Results: We found that inhibition of COX activity in the recipient mice prior to the injection of tumor cells decreased the percentage of the cells arrested in the lungs. This effect was highly significant since it subsequently led to substantial attenuation of lung metastasis development. Conclusion: These data thus demonstrate the antimetastatic effect of indomethacin through a mechanism which involves a reduction in tumor cell uptake by the lungs.

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“…Tumor cell arrest in the microvasculature is a critical event in hematogenous metastasis [43]. Following arrest and attachment to endothelial ceils, platelets rapidly associate with the arrested tumor cell, and then they disappear soon after tumor cell contact with the extracellular matrix is completed [44][45][46]. While associated with platelets, tumor cells induce endothelial cell retraction [44][45][46][47], spread on subendothelial matrix, release proteases and finally migrate through the subendothelial matrix [44,45].…”

Section: Tumor Cell Metastasismentioning

confidence: 99%

Fatty acid modulation of tumor cell-platelet-vessel wall interaction

et al. 1992

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Prostaglandins and other eicosanoids have been studied extensively in their physical, biochemical, biophysical and pharmacological aspects. However, studies on their role in tumor progression, especially metastases are relatively recent. Following a brief overview of the history of discovery and metabolism of eicosanoids and other fatty acids, we discuss the functions of these fatty acids (with emphasis on prostacyclin, thromboxane A2, 12-hydroxyeicosatetraenoic acid and 13-hydroxyoctadecadienoic acid) in cell transformation, tumor promotion and particularly in tumor cell metastasis. The relation between these monohydroxy fatty acids and tumor cell metastasis is discussed from three different perspectives, i.e., their effects on tumor cells, on platelets and on endothelial cells. The mechanism of these effects are then addressed at cell adhesion molecule, motility, protease, cell cytoskeleton, protein kinase and eicosanoid receptor levels. Finally, regulation of three key enzymes which generate eicosanoids (phospholipase, prostaglandin endoperoxide synthase and lipoxygenase) is explored.

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Analysis of the lodgement and extravasation of tumor cells in experimental models of hematogenous metastasis

Cited by 30 publications

References 42 publications

The Multiple Roles of Exosomes in Metastasis

The Multiple Roles of Exosomes in Metastasis

Indomethacin Inhibits the Accumulation of Tumor Cells in Mouse Lungs and Subsequent Growth of Lung Metastases

Fatty acid modulation of tumor cell-platelet-vessel wall interaction

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