Real-time <i>In vivo</i> Dual-color Imaging of Intracapillary Cancer Cell and Nucleus Deformation and Migration

Yamauchi, Kensuke; Yang, Meng; Jiang, Ping; Yamamoto, Norio; Xu, Mingxu; Amoh, Yasuyuki; Tsuji, Kazuhiko; Bouvet, Michael; Tsuchiya, Hiroyuki; Tomita, Katsuro; Moossa, A. R.; Hoffman, Robert M.

doi:10.1158/0008-5472.can-05-0069

Cited by 156 publications

(137 citation statements)

References 15 publications

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“…In addition, tumor cell deformability can contribute to their passage through narrow capillaries, which has been shown in our previous study and by others. 21,31 Although circulating tumor cells were observed throughout the 20-to 30-minute observation period, the numbers of arrested cells increased mainly during the initial 10 to 15 minutes, followed by a plateau-like shape of the curve. Both in liver and lung observed microvessels were not overloaded with arrested cells and, therefore, the question was raised whether specific characteristics of target organs might be responsible for this time dependence.…”

Section: Discussionmentioning

confidence: 99%

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Schlüter

Gaßmann

Enns

et al. 2006

The American Journal of Pathology

127

112

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Adhesive and invasive characteristics appear to be crucial for organ-specific metastasis formation. Using intravital microscopy we investigated the relation between the metastatic potential of colon carcinoma cells and their adhesive and invasive behavior during early steps of metastasis within microvasculatures of rat liver, lung, intestine, skin, muscle, spleen, and kidney in vivo. Colorectal carcinomas will affect ϳ6% of the population in the Western countries during their lifetime. These carcinomas are the third leading cause of cancer-related deaths among women and men and are the most important malignancies of the gut.1 Approximately 50% of the cancer patients die within 5 years because of cancerrelated problems, mostly attributable to metastatic lesions caused by the spread of cancers to near and distant sites. Even after potentially curative surgery, more than 30% of the patients with colorectal carcinomas subsequently develop metastases demonstrating that the spread from primary tumors to distant organs is usually the life-limiting aspect in colorectal carcinoma patients. 2Similar to other cancer entities, colorectal carcinomas often show organ preference of metastasis formation. The liver is the most common organ in which colorectal carcinomas establish distant metastases, and the liver is involved in more than 70% of patients with colorectal metastases. However, in 40 to 50% of these patients with liver metastases, other organs are also involved in metastatic colonization. The second most important organ for colorectal cancer metastasis is the lung, and 20 to 30% of all distant colorectal carcinoma metastases are found primarily in the lung. Isolated lung metastases with no evidence of other organ involvement are found in 5 to 10% of colorectal cancer patients. Other organs, such as the central nervous system, adrenal glands, spleen, skeleton, or skin together account for less than 10% of all colorectal metastases. 2,3The metastatic process consists of a number of sequential, interrelated steps that can all be rate limiting. 4,5 An important and early step during formation of distant metastasis appears to be the arrest of circulating tumor cells within the host organ.6,7 Approximately a century ago, two major hypotheses on the mechanisms of tumor cell arrest in metastatic host organs were proposed. Ewing 8 assumed that the random mechanical lodgment of Supported by the Innovative Medizinische Forschung Fund (University Hospital Mü nster) (Ha 1 2 01 01 to J.H.).K.S. and P.G. contributed equally to this study.

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Section: Discussionmentioning

confidence: 99%

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Schlüter

Gaßmann

Enns

et al. 2006

The American Journal of Pathology

127

112

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“…For RFP retrovirus production, the HindIII/NotI fragment from pDsRed2 (Clontech Laboratories, Inc., Palo Alto, CA), containing the full-length RFP cDNA, was inserted into the Hind III/NotI site of pLNCX2 (Clontech Laboratories) containing the neomycin resistance gene (4). PT67, an NIH3T3-derived packaging cell line (Clontech Laboratories) expressing the 10 Al viral envelope, was cultured in DMEM (Irvine Scientific, Santa Ana, CA) supplemented with 10% heat-inactivated fetal bovine serum (Gemini Bio-Products, Calabasas, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Previously, cancer cells were transfected with the Escherichia coli h-galactosidase (lacZ) gene, which enables detection of micrometastases in tissue sections. However, lacZ does not allow direct visualization of cancer cells in live animals (1)(2)(3)(4)(5). We developed an approach to visualizing cancer cells in vivo through the use of green fluorescent protein (GFP; refs.…”

Section: Introductionmentioning

confidence: 99%

Dual-Color Imaging of Nuclear-Cytoplasmic Dynamics, Viability, and Proliferation of Cancer Cells in the Portal Vein Area

et al. 2006

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We used dual-color in vivo cellular imaging to visualize trafficking, nuclear-cytoplasmic dynamics, and the viability of cancer cells after their injection into the portal vein of mice. For these studies, we used dual-color fluorescent cancer cells that express green fluorescent protein (GFP) linked to histone H2B in the nucleus and retroviral red fluorescent protein (RFP) in the cytoplasm. Human HCT-116-GFP-RFP colon cancer and mouse mammary tumor (MMT) cells were HCT-116-GFP-RFP in the portal vein of nude mice. The cells were observed intravitally in the liver at the single-cell level using the Olympus OV100 whole-mouse imaging system. Most HCT-116-GFP-RFP cells remained in sinusoids near peripheral portal veins. Only a small fraction of the cancer cells invaded the lobular area. Extensive clasmocytosis (destruction of the cytoplasm) of the HCT-116-GFP-RFP cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. Apoptosis was readily visualized in the dual-color cells by their altered nuclear morphology. The data suggest rapid death of HCT-116-GFP-RFP cells in the portal vein. In contrast, dual-color MMT-GFP-RFP cells injected into the portal vein mostly survived in the liver of nude mice 24 hours after injection. Many surviving MMT-GFP-RFP cells showed invasive figures with cytoplasmic protrusions. The cells grew aggressively and formed colonies in the liver. However, when the host mice were pretreated with cyclophosphamide, the HCT-116-GFP-RFP cells also survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the HCT-116-GFP-RFP cells but could not effectively kill the MMT-GFP-RFP cells. (Cancer Res 2006; 66(1): 303-6)

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“…Compression zones along the mid cell body Due to its membrane architecture, content and shape, the nucleus, although somewhat deformable, is considered as more voluminous and rigid structure than other regions of the cell [38,39]. In cancer cells moving through 3D fibrillar collagen, the cell diameter increases from the front and reaches its maximum at position of the nucleus (Fig.…”

Section: Proteolytic Structures During 3d Tissue Invasionmentioning

confidence: 99%

Mapping proteolytic cancer cell-extracellular matrix interfaces

Wolf

Friedl

2008

Clin Exp Metastasis

197

168

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For cancer progression and metastatic dissemination, cancer cells migrate and penetrate through extracellular tissues. Cancer invasion is frequently facilitated by proteolytic processing of components of the extracellular matrix (ECM). The cellular regions mediating proteolysis are diverse and depend upon the physical structure, composition, and dimensionality of the ECM contacted by the cell surface. Cancer cells migrating across 2D substrate contain proteolytic structures such as lamellipodia, invadopodia, and the trailing edge. Likewise, invasive mesenchymal migration through 3D fibrillar ECM, as monitored for HT1080 fibrosarcoma and MDA-MB-231 breast carcinoma cells by submicron-resolved imaging, is mediated by several types of proteolytic structures rich in filamentous actin, ß1 integrin, and MT1-MMP with distinct location and function. These comprise (i) anterior pseudopod bifurcataions and the nucleus corresponding to zones of local cell compression by constraining collagen fibers, (ii) lateral small spikes that protrude into the ECM and cause small spot-like proteolytic foci, and (iii) a strongly proteolytic trailing edge sliding along reorganized ECM fibers. Through their combined action these proteolytic surface structures cleave, remove, and realign ECM barriers, support rear end retraction, generate tube-like matrix defects and laterally widen existing tracks during 3D tissue invasion.

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Real-time In vivo Dual-color Imaging of Intracapillary Cancer Cell and Nucleus Deformation and Migration

Cited by 156 publications

References 15 publications

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Organ-Specific Metastatic Tumor Cell Adhesion and Extravasation of Colon Carcinoma Cells with Different Metastatic Potential

Dual-Color Imaging of Nuclear-Cytoplasmic Dynamics, Viability, and Proliferation of Cancer Cells in the Portal Vein Area

Mapping proteolytic cancer cell-extracellular matrix interfaces

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