Tumor Cell Interactions With the Microvasculature

Orr, F. W.; Wang, H. Helen

doi:10.1016/s1055-3207(18)30070-x

Cited by 69 publications

(44 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neo-angiogenesis, which is dependent on endothelial cell motility and invasion, is enhanced in xenograft models containing senescent fibroblasts [50]. Further, IL-1, which is a SASP component, is known to activate the endothelium and consequently increases the adhesiveness of cancer cells to blood vessel walls [52]. Thus, senescent cells might promote extravasation of cancer cells to secondary metastatic sites.…”

Section: Effects Of the Sasp On Cell Migration And Invasionmentioning

confidence: 99%

Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts

Laberge

Awad

Campisi

et al. 2011

Cancer Microenvironment

207

154

View full text Add to dashboard Cite

Depending on the cell type and tissue environment, epithelial and mesenchymal cell phenotypes are not static and can be highly dynamic. Epithelial-mesenchymal transitions (EMTs) and reverse EMTs provide flexibility during embryogenesis. While EMTs are a critical normal process during development and wound healing, properties of the EMT have been implicated in human pathology, particularly cancer metastasis. A normal undamaged epithelium does not typically exhibit features of an EMT. However, particularly under the influence of the surrounding microenvironment, cancer cells may reactivate developmental phenotypes out of context in the adult. This reactivation, such as the EMT, can facilitate tumor cell invasion and metastasis, and therefore is a major mechanism of tumor progression. Conversely, cellular senescence, which is associated with aging, is a process by which cells enter a state of permanent cell cycle arrest, thereby constituting a potent tumor suppressive mechanism. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescenceassociated secretory phenotype (SASP) that turns senescent fibroblasts into pro-inflammatory cells having the ability to promote tumor progression, in part by inducing an EMT in nearby epithelial cells. Here, we summarize the potential impacts of SASP factors, particularly interleukins, on tissue microenvironments and their ability to stimulate tumor progression through induction of an EMT.

show abstract

Section: Effects Of the Sasp On Cell Migration And Invasionmentioning

confidence: 99%

Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts

Laberge

Awad

Campisi

et al. 2011

Cancer Microenvironment

207

154

View full text Add to dashboard Cite

show abstract

“…Interactions between intravascular cancer cells and the endothelium are important determinants of metastatic outcome. 1,2 For example, the expression of constitutive and inducible microvascular adhesion molecules, and the release of reactive oxygen species (NO, O 2 Ϫ , and H 2 O 2 ) by endothelial cells or cancer cells can regulate the mechanisms that govern the metastatic process, including cancer cell adhesion and arrest, 3 the production of endothelial matrix metalloproteinases, 4 and cancer cell apoptosis. 5 Evidence from in vitro and in vivo studies has shown that reactive oxygen and nitrogen species can be cytotoxic to neoplastic cells 6 -9 and reduced their adhesion to postcapillary venules.…”

Section: Metastatic Cancer Cells Seed the Lung Via Blood Vesselsmentioning

confidence: 99%

Arrest of B16 Melanoma Cells in the Mouse Pulmonary Microcirculation Induces Endothelial Nitric Oxide Synthase-Dependent Nitric Oxide Release that Is Cytotoxic to the Tumor Cells

Qiu

Orr

Jensen

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

Metastatic cancer cells seed the lung via blood vessels. Because endothelial cells generate nitric oxide (NO) in response to shear stress, we postulated that the arrest of cancer cells in the pulmonary microcirculation causes the release of NO in the lung. After intravenous injection of B16F1 melanoma cells, pulmonary NO increased sevenfold throughout 20 minutes and approached basal levels by 4 hours. NO induction was blocked by N G -nitro-L-arginine methyl ester (L-NAME) and was not observed in endothelial nitric oxide synthase (eNOS)-deficient mice. NO production, visualized ex vivo with the fluorescent NO probe diaminofluorescein diacetate, increased rapidly at the site of tumor cell arrest, and continued to increase throughout 20 minutes. Arrested tumor cells underwent apoptosis with apoptotic counts more than threefold over baseline at 8 and 48 hours. Neither the NO signals nor increased apoptosis were seen in eNOS knockout mice or mice pretreated with L-NAME. At 48 hours, 83% of the arrested cells had cleared from the lungs of wild-type mice but only ϳ55% of the cells cleared from eNOS-deficient or L-NAME pretreated mice. eNOS knockout and L-NAME-treated mice had twofold to fivefold more metastases than wild-type mice, measured by the number of surface nodules or by histomorphometry. We conclude that tumor cell arrest in the pulmonary microcirculation induces eNOS-dependent NO release by the endothelium adjacent to the arrested tumor cells and that NO is one factor that causes tumor cell apoptosis, clearance from the lung, and inhibition of metastasis. In the lung, metastatic neoplasms are the most common malignant tumors. Their formation usually involves hematogenous seeding of metastatic cancer cells into the lung from remote primary tumors. Interactions between intravascular cancer cells and the endothelium are important determinants of metastatic outcome. 1,2 For example, the expression of constitutive and inducible microvascular adhesion molecules, and the release of reactive oxygen species (NO, O 2 Ϫ , and H 2 O 2 ) by endothelial cells or cancer cells can regulate the mechanisms that govern the metastatic process, including cancer cell adhesion and arrest, 3 the production of endothelial matrix metalloproteinases, 4 and cancer cell apoptosis. 5 Evidence from in vitro and in vivo studies has shown that reactive oxygen and nitrogen species can be cytotoxic to neoplastic cells 6 -9 and reduced their adhesion to postcapillary venules. 10 In vivo, we have recently demonstrated that the arrest of intravascular B16F1 melanoma cells in the liver induces the rapid local release of nitric oxide (NO) that causes apoptosis of the melanoma cells and inhibits their subsequent development into hepatic metastases. 5 Because pulmonary endothelial cells generate NO in response to shear stress, 11 we have postulated that there is a comparable cytotoxic mechanism in the lung.Here we provide data showing that the arrest of B16F1 melanoma cells in the pulmonary circulation of wild-type C57B1/6 mice (WT mice) induces the ...

show abstract

“…Initially, a decrease in homotypic and heterotypic cancer cell adhesion, caused by the reduced expression of E-cadherins and elevated activity of proteolytic enzymes, including numerous metalloproteinases, promotes their escape from a primary tumor and intravasation (3,4). During postintravasation stages, however, the increased ability of blood-borne metastatic cells to engage into new heterotypic and homotypic adhesive interactions could be critically important for establishing secondary lesions in distant tissues and organs (5,6). Two major theories describing cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, emphasize heterotypic tumor cell adhesion to blood vessel endothelia and homotypic cancer cell aggregation as corresponding key components of the metastatic cascade (reviewed in Ref.…”

Section: Introductionmentioning

confidence: 99%

“…Neoplastic cell heterotypic adhesion to the microvascular endothelium, resulting in tumor cell arrest in the vasculature of a target organ, is an essential early step in hematogenous cancer spread (5). Recent observations, suggesting that only endothelium-attached malignant cells are capable of giving rise to hematogenous cancer metastases, strongly support this idea (8).…”

Section: Introductionmentioning

confidence: 99%

Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium

Glinsky

Glinskii

et al. 2004

Urologic Oncology: Seminars and Original Investigations

172

197

View full text Add to dashboard Cite

The two major theories of cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, view tumor cell adhesion to blood vessel endothelia and cancer cell aggregation as corresponding key components of the metastatic process. Here, we demonstrate in vitro, ex vivo, and in vivo that metastatic breast and prostate carcinoma cells form multicellular homotypic aggregates at the sites of their primary attachment to the endothelium. Our results suggest that metastatic cell heterotypic adhesion to the microvascular endothelium and homotypic aggregation represent two coordinated subsequent steps of the metastatic cascade mediated largely by similar molecular mechanisms, specifically by interactions of tumor-associated Thomsen-Friedenreich glycoantigen with the ␤-galactoside-binding protein, galectin-3. In addition to inhibiting neoplastic cell adhesion to the endothelium and homotypic aggregation, disrupting this line of intercellular communication using synthetic ThomsenFriedenreich antigen masking and Thomsen-Friedenreich antigen mimicking compounds greatly affects cancer cell clonogenic survival and growth as well. Thus, ␤-galactoside-mediated intravascular heterotypic and homotypic tumor cell adhesive interactions at the sites of a primary attachment to the microvascular endothelium could play an important role during early stages of hematogenous cancer metastasis.

show abstract

Tumor Cell Interactions With the Microvasculature

Cited by 69 publications

References 87 publications

Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts

Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts

Arrest of B16 Melanoma Cells in the Mouse Pulmonary Microcirculation Induces Endothelial Nitric Oxide Synthase-Dependent Nitric Oxide Release that Is Cytotoxic to the Tumor Cells

Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium

Contact Info

Product

Resources

About