Experimental lymphatic metastasis

Carr, Ian

doi:10.1111/j.1365-2818.1983.tb04247.x

Cited by 19 publications

(12 citation statements)

References 11 publications

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“…Since no comparable loss is indicated for axillary and paraaortic nodes transplanted with this number of cells (Figure 4a), and it also occurs for inguinal nodes left in the primary host (Figure 4b) it is most unlikely to be an artefact. Qualitatively similar changes in the number of metastatic cells passing through the prepopliteal nodes draining the footpad of rats given 2 x 107 Walker carcinoma cells 6 days previously has also been reported (Carr & Carr, 1981). Hewitt and Blake (1975) have also shown, using the isogeneic WHT carcinoma, that the translymphnodal passage of spontaneously disseminated cells may occur.…”

Section: The Transplantation Of Metastatic Cellssupporting

confidence: 50%

“…As indicated by Porter et al (1973), a limiting dilution (TD50) assay would be helpful in the study of tumour metastasis but, presumably due to the previous lack of a suitable animal model (Carr & Carr, 1981;Fidler & Hart, 1982;Kim, 1984;Vandenris et al, 1985) . More importantly the method adopted was similar to a dilution assay but to avoid the need to isolate metastatic cells from a node, their numbers were assayed by determining the latency of the tumour it formed after transplantation to a fresh host.…”

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confidence: 99%

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The lymphnodal clonogenicity and kinetics of metastatic cells disseminated by a transplanted rat carcinoma

Dixon¹,

Bagnall²,

Speakman³

1986

Br J Cancer

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In contrast to the wealth of data on the cellular transplantation of experimental tumours there are few concerning the further seeding of cells that may be released once tumour growth is established in situ. In particular, the lack of an in vivo clonogenic assay for spontaneous metastatic cells has limited therapeutic studies of this aspect of the cancer problem to the experimental use of clinical endpoints, e.g. prolonged survival or increased survival rates (Van de Velde et al., 1977;De Ruiter et al., 1982;Wondergem et al., 1985). In the 1950s methods for assaying the clonogenicity and transplantation kinetics of primary tumour cells were developed (Hewitt, 1958;Berry & Andrews, 1961) and this produced rapid progress in quantifying the principal factors governing the clinical outcome of primary tumour therapy (Steel, 1977). A similar development in experimental tumour metastasis could be just as important, e.g. in defining the basic principles of adjuvant treatment of patients at significant risk from occult metastases (Salmon, 1977).As indicated by Porter et al. (1973), a limiting dilution (TD50) assay would be helpful in the study of tumour metastasis but, presumably due to the previous lack of a suitable animal model (Carr & Carr, 1981;Fidler & Hart, 1982;Kim, 1984;Vandenris et al., 1985) . More importantly the method adopted was similar to a dilution assay but to avoid the need to isolate metastatic cells from a node, their numbers were assayed by determining the latency of the tumour it formed after transplantation to a fresh host. From the latency and incidence of tumour positive nodes, it is also possible to derive a TD50 curve for metastatic cells and thus provide the basis of an in situ cell survival assay after therapy (Speakman, 1986). In this paper we present and discuss our data on the lymphnodal clonogenicity of untreated metastatic cells. All the data were derived from only a few LMC1 generations using liquid-N2 stored material and no changes in tumour transplantability or growth characteristics were observed. Three types of experiment were performed. The first to determine the TD50 of LMC1 cells derived directly from the primary tumour. The second involved the transfer of axillary, inguinal and para-aortic lymph nodes from tumour-bearing to fresh hosts to determine from the incidence and latency of tumours formed the TD50 of transplanted metastatic cells. In the third, the subcutaneous primary tumour was excised at various times after its implantation, leaving the nodes to form overt metastases and thus determine their incidence and latency in the primary host.

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Section: The Transplantation Of Metastatic Cellssupporting

confidence: 50%

mentioning

confidence: 99%

The lymphnodal clonogenicity and kinetics of metastatic cells disseminated by a transplanted rat carcinoma

Dixon¹,

Bagnall²,

Speakman³

1986

Br J Cancer

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“…The dissemination of coherent masses of tumor satellites is histologically observed in tumors of epithelial origin (e.g., invasive oral carcinoma and adenocarcinoma) or melanoma [154]. In vivo, such coherent cell groups retain desmosomes and other cell-cell junctions [163], protrude into the tissue preferentially along paths of least resistance such as clefts, natural cleavage planes or tissue spaces (e.g., fiber bundles, nerves, blood vessels) [83] and can be detected in lymphatic vessels [164] and in peripheral blood [165,166]. Using time-lapse videomicroscopy, the coordinated protrusion, detachment, and migration of neoplastic cell clusters from primary tumor explants is seen upon culture in 3-D collagen lattices [99,126].…”

Section: Cellular Pattern Of Tumor Cell Migrationmentioning

confidence: 99%

The biology of cell locomotion within three-dimensional extracellular matrix

Friedl

Bröcker

2000

Cellular and Molecular Life Sciences (CMLS)

589

463

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Cell migration in three-dimensional (3-D) extracellular matrix (ECM) is not a uniform event but rather comprises a modular spectrum of interdependent biophysical and biochemical cell functions. Haptokinetic cell migration across two-dimensional (2-D) surfaces consists of at least three processes: (i) the protrusion of the leading edge for adhesive cell-substratum interactions is followed by (ii) contraction of the cell body and (iii) detachment of the trailing edge. In cells of flattened morphology migrating slowly across 2-D substrate, contact-dependent clustering of adhesion receptors including integrins results in focal contact and stress fiber formation. While haptokinetic migration is predominantly a function of adhesion and deadhesion events lacking spatial barriers towards the advancing cell body, the biophysics of the tissues require a set of cellular strategies to overcome matrix resistance. Matrix barriers force the cells to adapt their morphology and change shape and/or enzymatically degrade ECM components, either by contact-dependent proteolysis or by protease secretion. In 3-D ECM, in contrast to 2-D substrate, the cell shape is mostly bipolar and the cytoskeletal organization is less stringent, frequently lacking discrete focal contacts and stress fibers. Morphologically large spindle-shaped cells (i.e., fibroblasts, endothelial cells, and many tumor cells) of high integrin expression and strong cytoskeletal contractility utilize integrin-dependent migration strategies that are coupled to the capacity to reorganize ECM. In contrast, a more dynamic ameboid migration type employed by smaller cells expressing low levels of integrins (i.e., T lymphocytes, dendritic cells, some tumor cells) is characterized by largely integrin-independent interaction strategies and flexible morphological adaptation to preformed fiber strands, without structurally changing matrix architecture. In tumor invasion and angiogenesis, migration mechanisms further comprise the migration of entire cell clusters or strands maintaining stringent cell-cell adhesion and communication while migrating. Lastly, cellular interactions, enzyme and cytokine secretion, and tissue remodeling provided by reactive stroma cells (i.e. fibroblasts and macrophages) contribute to cell migration. In conclusion, depending on the cellular composition and tissue context of migration, diverse cellular and molecular migration strategies can be developed by different cell types.

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“…It has been recently suggested that stromal fibroblasts and endothelial cells may acquire genetic alterations similar to those seen in tumor cells and this coevolution may provide growth and migratory advantages to both cell types (Pelham et al 2006). In vivo, migrant cell clusters retain cell-cell junctions, protrude into adjacent tissue driven by leading "pathfinder" cells, and can be detected in lymphatic vessels (Carr 1983) and in peripheral blood (Liotta et al 1976;Brandt et al 1996;Friedl and Brocker 2000). Such coordinated cell migration of neoplastic cell clusters from primary explants can also be visualized using time-lapse videomicroscopy in three-dimensional (3D) collagen matrices (Friedl et al 1995).…”

Section: Migratory Neighbors and Distant Invaders Genes And Developmentmentioning

confidence: 99%

Migratory neighbors and distant invaders: tumor-associated niche cells

Wels

Kaplan²,

Rafii³

et al. 2008

Genes Dev.

357

302

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The cancer environment is comprised of tumor cells as well as a wide network of stromal and vascular cells participating in the cellular and molecular events necessary for invasion and metastasis. Tumor secretory factors can activate the migration of host cells, both near to and far from the primary tumor site, as well as promote the exodus of cells to distant tissues. Thus, the migration of stromal cells and tumor cells among specialized microenvironments takes place throughout tumor and metastatic progression, providing evidence for the systemic nature of a malignancy. Investigations of the tumor-stromal and stromal-stromal cross-talk involved in cellular migration in cancer may lead to the design of novel therapeutic strategies.Understanding the complex biological networks at play in metastasis requires a precise detailing of the molecular and cellular pathways involved in local and systemic migration. The long prevailing model of invasion and metastasis has focused on the adhesive and migratory capabilities that are intrinsic to tumor cells (Hanahan and Weinberg 2000). Meanwhile, we are becoming increasingly aware that tumors are composed of genetically altered malignant cells along with a heterogeneous population of stromal cells, whose dynamic interactions can profoundly enhance tumor progression and metastasis. Through the production of chemokines, growth factors, and matrix-degrading enzymes (Table 1), supportive cells-including fibroblasts, immune cells, and bone marrow (BM)-derived stem and progenitor cells-support blood vessel formation, break down basement membrane barriers, and attract tumor cells to distant sites. Tumor cells are constantly giving instructions, not only by direct cell-cell interactions, but also by secreted factors that "activate" normal host cells at both proximal and distal sites to migrate, eventually developing permissive niches that, in return, promote tumor cell survival and proliferation. The focus of this review is on the cellular constituents of the primary and metastatic tumor microenvironments, with emphasis on their migratory pathways. We hope to convey that the tumor and host cell interaction is truly reciprocal; while host cells may support tumor cells, tumor cells in turn modulate the microenvironments within which they reside. Furthermore, we highlight that cancer is a systemic disease, encompassing collective cell movements of tumor and stromal cells that are a prerequisite for tumor cell invasion and metastasis. Intrinsic tumor cell migratory capabilitiesInherent to the metastatic process is the capability of tumor cells to migrate through connective tissue barriers comprising cell-cell adherent junctions, basement membranes, and interstitial tissue stroma. This intrinsic migratory behavior is highly dependent on the interplay between adhesive and proteolytic activities. Tumor cell down-regulation of proteins mediating cell-cell interactions, such as cadherins, leads to changes in cell signaling, actin-based cytoskeletal structure, and eventual dissociation from n...

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Experimental lymphatic metastasis

Cited by 19 publications

References 11 publications

The lymphnodal clonogenicity and kinetics of metastatic cells disseminated by a transplanted rat carcinoma

The lymphnodal clonogenicity and kinetics of metastatic cells disseminated by a transplanted rat carcinoma

The biology of cell locomotion within three-dimensional extracellular matrix

Migratory neighbors and distant invaders: tumor-associated niche cells

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