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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When cancer cells spread away from the primary tumor, they often follow the trajectories of lymphatic vessels, nerves, white matter tracts, or other heterogeneous structures in tissues. To better understand this form of guided cell migration we designed a series of microfluidic devices that mechanically constrain migrating cancer cells inside microchannels with cross-section comparable to cell size. We observed unexpectedly fast and persistent movement in one direction for several hours of cancer cells of different types. The persistent motility occurs spontaneously, in the absence of external gradients, suggesting the presence of intrinsic mechanisms driving cancer cell motility that are induced in conditions of mechanical confinement. To probe the mechanisms responsible for this behavior, we exposed cancer cells inside channels to drugs targeting the microtubules, and measured a significant reduction in the average migration speed. Surprisingly, a small number of cells appeared not to be affected by the treatment and displayed fast and persistent migration, comparable to the untreated cells. The new matrix-free, 3D-confined motility assay replicates critical interactions that cancer cells would normally have inside tissues, is compatible with high-content, high-throughput analysis of cellular motility at single cell level, and could provide useful insights into the biology of cancer cell migratory phenotype.
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PMID:Spontaneous migration of cancer cells under conditions of mechanical confinement. 2002 65

MMP11 expression is a poor prognosis factor in human carcinomas. Although it has been shown to favor primary tumor development, its role in metastatic processes remains unclear. We studied the hematogenous metastatic activity of C26 mouse colon cancer cells injected into the tail vain of wild-type or MMP11-deficient mice during 2 months. Using X-ray computed tomography to image metastasis development in recipient living mice, lung metastases were found to occur earlier and to grow faster in wild-type mice. Histological analyses of the lung, liver, kidney, adrenal gland, mammary gland, ovary and salivary gland, performed at the end of experiment, also showed lower numbers of metastases in wild-type mice, regardless of organ. Lung metastases showed similar Factor VIII-positive vascular networks regardless of the mouse MMP11 status. However, those found in MMP11-deficient mice also exhibited vessel-like structures that did not express Factor VIII, Lyve-1 and vimentin, and were not stained with PAS. Consequently, they did not correspond to vascular or lymphatic vessels or to vascular mimicry channels. Collectively, these results revealed significant spatio-temporal variability that is dependent on host MMP11 status. Furthermore, they point-out the paradoxical role of MMP11 in favoring the onset and growth of lung metastases but limiting lung foci number, and inhibiting the cancer cell dissemination to other organs. These data highlight the complexity of the metastatic process in which the same factor can play activator or repressor functions depending on the metastatic step.
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PMID:Matrix metalloproteinase 11/stromelysin-3 exerts both activator and repressor functions during the hematogenous metastatic process in mice. 2020 94

The classical model of metastasis is that tumor cell dissemination occurs late in tumor development, after the primary tumor has grown, and that only then will tumor cells invade the local tissue, enter the blood or lymphatic vessels, and colonize new sites to cause metastases. However, evidence increasingly indicates that single tumor cells spread to distant sites much earlier than previously believed. In this issue of the JCI, Eyles and colleagues provide new insight into the mechanisms underlying early tumor cell dissemination, formation of metastases, and tumor immunosurveillance using transgenic mice that spontaneously develop melanomas of the uvea. The authors provide striking evidence that tumor cells start to disseminate during the initial steps of tumor development, that late appearing metastases arise from these early disseminated tumor cells, and that CD8+ T cells inhibit the growth of disseminated tumor cells, surprisingly, not by cytotoxic effects, but through cytostatic effects.
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PMID:Early tumor dissemination, but late metastasis: insights into tumor dormancy. 2050 44

Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels. Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.
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PMID:Lymphangiogenesis, lymphatic endothelial cells and lymphatic metastasis in head and neck cancer--a review of mechanisms. 2069 Apr 13

Lymphatic metastasis plays a critical role in ovarian cancer, indicates poor prognoses and correlates to the majority of cancer deaths. Camptothecin derivatives exhibit promising activity for the treatment of solid tumors because of its specific inhibition of eukaryotic DNA topoisomerase I. Yet, its application is hindered due to extreme water insolubility and severe side effects. It is essential to establish an efficient and safe protocol for the administration of camptothecin versus tumor metastasis and growth. In the current research, we encapsulated camptothecin with N-trimethyl chitosan (CPT-TMC) to increase its water-solubility and lower its side effects, and tested it on a high potential lymphogenous metastatic model of human ovarian cancer. In the prophase study, we successfully transfected SKOV3 cells with VEGF-D recombinant plasmid DNA (pcDNA3.1(+)/VEGF-D) to construct a cell line named SKOV3/VEGF-D and establish a feasible lymphogenous metastatic model. The antitumor and antimetastatic activities of CPT-TMC were evaluated in nude mice subcutaneously inoculated with SKOV3/VEGF-D cells at the left hindlimb claw pad. The tumor-bearing mice were divided randomly into four groups and treated twice per week for three weeks. Evan's Blue Dye was used to delineate functional lymphatic vessels. Lymphatic metastasis rates were detected by hematoxylin and eosin (HE) staining. Expression of VEGF-D and MMP-9 were investigated by immunohistochemistry. In contrast to controls, administration of CPT-TMC achieved effective inhibition in primary tumor volume and lymphogenous metastasis, yet without apparent systemic toxic effects. These effects were associated with simultaneously down-regulated VEGF-D and MMP-9 expression, significantly decreased tumor-associated lymphatic and blood sprouts, tremendously reduced systemic toxic effects, dramatically increased tumor apoptotic index. Our data indicate that CPT-TMC is superior to CPT by maximizing its anticancer and antimetastatic activities with minimal toxicity on hosts. CPT-TMC may become a potentially therapeutic strategy against human advanced ovarian cancer.
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PMID:The antitumor and antimetastatic effects of N-trimethyl chitosan-encapsulated camptothecin on ovarian cancer with minimal side effects. 2081 74

During breast cancer metastasis cells emigrate from the primary tumor to the bloodstream, and this carries them to distant sites where they infiltrate and sometimes form metastases within target organs. These cells must penetrate the dense extracellular matrix comprising the basement membrane of the mammary duct/acinus and migrate toward blood and lymphatic vessels, processes that mammary tumor cells execute primarily using epidermal growth factor (EGF)-dependent protrusive and migratory activity. Here, we focus on how the actin regulatory protein Mena affects EGF-elicited movement, invasion and metastasis. Recent findings indicate that, in invasive migratory tumor cells, Mena isoforms that endow heightened sensitivity to EGF and increased protrusive and migratory abilities are upregulated, whereas other isoforms are selectively downregulated. This change in Mena isoform expression enables tumor cells to invade in response to otherwise benign EGF stimulus levels and could offer an opportunity to identify metastatic risk in patients.
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PMID:Metastasis: tumor cells becoming MENAcing. 2107 Dec 26

The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology.
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PMID:Platelets: covert regulators of lymphatic development. 2107 6

The circulatory system comprises a tubular network of blood vessels including arterioles, capillaries, venules, and lymphatic vessels. This circulatory system is essential for the embryonic development and maintenance of all tissues, which requires the transportation of oxygen, carbon dioxide, and nutrition. The system regulates the movement of fluid into and out of organs with high level of efficiency. "Tumor angiogenesis" describes the rapid growth of certain components of the circulatory system in an abnormal fashion that is both heterogeneous and dysregulated. The aberrant flow between abnormal tumor vessels and normal vessels poses a high risk for seeding of potentially metastatic cancer cells. Moreover, it has also been reported that premetastatic distant organ vessels already undergo specific changes due to the presence of a remote primary tumor. Therapeutic strategies aimed at targeting tumor vessels have the potential to suppress tumor growth, and also influence the effects of tumor-derived cytokines and circulating tumor cells. Furthermore, focusing on vessels in a premetastatic organ that have responded to a primary tumor may be one possibility for reducing metastatic risk.
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PMID:Vasculogenensis, angiogenesis and special features of tumor blood vessels. 2119 39

The dissemination of tumor cells to sites far from the primary tumor (metastasis) is the principal cause of death in cancer patients. Tumor-associated lymphatic vessels are a key conduit for metastatic tumor cells, which typically first colonize the lymph nodes. Although the primary tumor and affected lymph nodes can be removed during surgery, tumor cells inside lymphatic vessels are left behind. Here, we show that in-transit tumor cells inside lymphatic vessels in mice bearing mouse melanomas or human lung tumors give rise to metastases. Using photodynamic therapy with the benzoporphyrin derivative verteporfin, we selectively destroyed lymphatic vessels in mice and pigs. Destruction of tumor-associated lymphatic vessels also eradicated intralymphatic tumor cells and prevented metastasis of mouse melanoma cells and subsequent relapse. Photodynamic therapy, when combined with anti-lymphangiogenic therapy, prevented further tumor invasion of lymphatic vessels. These findings highlight the potential of targeting in-transit tumor cells in patients.
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PMID:Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis. 2130 1

Tumors usually reach secondary sites via blood vessels or lymphatic vessels. Two processes dependent upon cell migration speed metastasis by reducing the distance between the primary tumor and these vessels. The first process is invasion, in which cancer cells migrate toward the capillaries. The second is angiogenesis, blood vessel growth into the primary tumor, which has been proved to promote blood-borne tumor spread by reducing the invasive distance, and may also aid lymphatic metastasis. Angiogenesis is dependent on endothelial cell migration. When studying the spread of tumors to secondary sites, it is therefore important to understand: (1) the response of tumor cell lines to motility boosting factors and (2) endothelial cell chemotaxis in response to tumor-derived angiogenic factors.
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PMID:Cell migration and the boyden chamber. 2134 Aug 46


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