Realtime visualization of tumor cell/endothelial cell interactions during transmigration across the endothelial barrier

Heyder, Christoph; Gloria-Maercker, Eva; Entschladen, Frank; Hatzmann, Wolfgang; Niggemann, Bernd; Zänker, K. S.; Dittmar, Thomas

doi:10.1007/s00432-002-0377-7

Cited by 50 publications

(28 citation statements)

References 16 publications

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“…These observations are consistent with study by Burns et al 7 for the neutrophil migration across HUVEC monolayers, suggesting a similar mechanism by which TCs and leukocytes accomplish their transmigration across microvessel walls. These results are also consistent with our previous study on TC adhesion to bEnd3 monolayers 19 , suggesting that adhesion is the initial step for TC extravasation 30, 37, 60 .…”

Section: Discussionsupporting

confidence: 93%

“…Many previous studies investigated TC adhesion to microvessel walls as the initial step for extravasation 30, 37, 60 . Using an in vitro real-time model, Heyder et al 31 demonstrated that invasive human bladder carcinoma cell line T24 irreversibly damages the ECs by inducing apoptosis at the site of TC infiltration.…”

Section: Introductionmentioning

confidence: 99%

“…Most recently, Joen et al 32 developed an organ-specific 3D microfluidic model to elucidate the effects of microenvironments on the extravasation of MDA-MB-231 cells and they found that the leakiest environment gave rise to the lowest extravasation rate. In terms of TC adhesion and transmigration locations, previous studies reported that TCs can transmigrate through both the para- and trans-EC pathways 3, 20, 29, 30, 56, 59 .…”

Section: Introductionmentioning

confidence: 99%

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Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium

Fan

2015

Ann Biomed Eng

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Tumor cell extravasation through the endothelial barrier forming the microvessel wall is a crucial step during tumor metastasis. However, where, how and how fast tumor cells transmigrate through endothelial barriers remain unclear. Using an in vitro transwell model, we performed a transmigration assay of malignant breast tumor cells (MDA-MB-231) through brain and lung microvascular endothelial monolayers under control and pathological conditions. The locations and rates of tumor cell transmigration as well as the changes in the structural components (integrity) of endothelial monolayers were quantified by confocal microscopy. Endothelial monolayer permeability to albumin Palbumin was also quantified under the same conditions. We found that about 98% of transmigration occurred at the joints of endothelial cells instead of cell bodies; tumor cell adhesion and transmigration degraded endothelial surface glycocalyx and disrupted endothelial junction proteins, consequently increased Palbumin; more tumor cells adhered to and transmigrated through the endothelial monolayer with higher Palbumin; Palbumin and tumor transmigration were increased by vascular endothelial growth factor (VEGF), a representative of cytokines, and lipopolysaccharides (LPS), a typical systemic inflammatory factor, but reduced by adenosine 3′, 5′-cyclic monophosphate (cAMP). These results suggest that reinforcing endothelial structural integrity is an effective approach for inhibiting tumor extravasation.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium

Fan

2015

Ann Biomed Eng

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“…It is also difficult to predict how changes in stiffness between the PDMS and gel affect extravasation mechanisms. Furthermore, most studies of extravasation or TEM across planar EC monolayers 12, 13, 15, 16 are limited in their physiological relevance.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of tumor cell extravasation in an in vitro microvascular network platform

et al. 2013

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“…administration. The extravasation of tumor cell clusters derived from the invasive human bladder carcinoma cell line T24 occurs in a relatively short time-frame up to 4 h after adhesion to the endothelium [24], suggesting that melanoma cells inoculated i.v. are also trapped and adhered to endothelium in the lung and then extravasate from the vein within a few hours.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase inhibitor, MMI270 (CGS27023A) inhibited hematogenic metastasis of B16 melanoma cells in both experimental and spontaneous metastasis models

Kasaoka

Nishiyama

Okada

et al. 2008

Clin Exp Metastasis

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Matrix metalloproteinases (MMP) have been implicated in several steps of tumor metastasis, such as invasion in the extracellular matrix, intravasation, extravasation, and growth in a distant organ site. Various synthetic MMP inhibitors have been reported to suppress tumor metastasis in animal models. However, there are few reports describing which steps in the metastasis process are most critical for inhibition by MMP inhibitors. In the experimental lung colonization model by i.v. injection of mouse B16-F10 melanoma cells, we found that the daily administration of MMI270 for 2 weeks significantly decreased the number of colonies in the lung compared with the control without affecting the size of colony. Micrometastasis was monitored day 7 post-inoculation by measuring the melanin content in the lung as well as by microscopic examination of the lung tissue sections. Even only twice administrations of MMI270 on the first day after tumor injection significantly inhibited micrometastasis in the lung. In the spontaneous metastasis model using B16-BL6 melanoma cells, lung metastasis was not affected by a continuous administration of MMI270 using a mini osmotic-pump. On the contrary, when mice were subjected to popliteal lymphadenectomy on day 7 after the cell inoculation in the footpad subdermis, the continuous administration of MMI270 significantly suppressed the lung metastasis. These results suggest that the tumor cell extravasation in the target organ is the most critical step where MMPs can play their significant role in the experimental metastasis, and that the lymphatic metastasis process is less susceptible to MMI270 than the hematogenic metastasis process in the spontaneous metastasis model.

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Realtime visualization of tumor cell/endothelial cell interactions during transmigration across the endothelial barrier

Abstract: Realtime laser scanning confocal microscopy leads to a better understanding of the complex and dynamic cell-to-cell and cell-to-matrix interactions during the extravasation process.

Cited by 50 publications

References 16 publications

Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium

Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium

Mechanisms of tumor cell extravasation in an in vitro microvascular network platform

Matrix metalloproteinase inhibitor, MMI270 (CGS27023A) inhibited hematogenic metastasis of B16 melanoma cells in both experimental and spontaneous metastasis models

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