Interaction of Activated Natural Killer Cells with Normal and Tumor Vessels in Cranial Windows in Mice

Melder, Robert J.; Salehi, Hassan A.; Jain, Rakesh K.

doi:10.1006/mvre.1995.1036

Cited by 38 publications

(17 citation statements)

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“…This number also has been confirmed in LS174T tumors grown in the ovarian pedicle (22). We also know that the vascular surface area of the LS174T tumor is approximately 370 cm 2 ͞cm Other evidence that fits our hypothesis comes from studies of lymphocyte adhesion that show preferential adhesion of activated natural killer (A-NK) cells in tumors (7,24,25). It is intriguing that a high level of adhesion occurs in only 10% of the vessels (24).…”

Section: Discussionsupporting

confidence: 74%

“…We also know that the vascular surface area of the LS174T tumor is approximately 370 cm 2 ͞cm Other evidence that fits our hypothesis comes from studies of lymphocyte adhesion that show preferential adhesion of activated natural killer (A-NK) cells in tumors (7,24,25). It is intriguing that a high level of adhesion occurs in only 10% of the vessels (24). Our results are consistent with the hypothesis that these A-NK cells bind to the luminally exposed tumor cells, as the number of mosaic vessels in the examined tumors is on the order of 10%.…”

Section: Discussionsupporting

confidence: 71%

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Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood

Chang

Tomaso

McDonald

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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605

382

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The presence of ''mosaic'' vessels in which both endothelial cells and tumor cells form the luminal surface has profound implications for metastasis, drug delivery, and antivascular therapy. Yet little is known of the frequency, and thus importance, of mosaic vessels in tumors. Using CD31 and CD105 to identify endothelial cells and endogenous green fluorescent protein labeling of tumor cells, we show that Ϸ15% of perfused vessels of a colon carcinoma xenografted at two different sites in mice were mosaic vessels having focal regions where no CD31͞CD105 immunoreactivity was detected and tumor cells appeared to contact the vessel lumen. These regions occupied Ϸ25% of the perimeter of the mosaic vessels, or Ϸ4% of the total vascular surface area in these colon carcinomas. In addition, we found similar numbers of mosaic vessels in human colon carcinoma biopsies. Our results are consistent with the observation that Ϸ10 6 cells are shed daily per g of tumor. More importantly, our data offer a possible explanation for the antivascular effects of cytotoxic agents and suggest potential strategies for targeting the tumor vasculature. Many reports over the past five decades have claimed that cancer cells are located in the walls of tumor blood vessels. This idea was presented as early as 1948 (1), and ultrastructural evidence of tumor-lined vessels was reported in the 1960s by Warren and Shubik (2) and by others in the 1980s (3, 4). This issue also has been addressed in reviews on tumor blood f low (5) and in textbooks of general pathology (6). Sasaki et al. (7) proposed that cancer cells in these vessels might be the sites of adhesion of activated natural killer (A-NK) cells, and more recently, a controversial study by Maniotis et al. (8) concluded that certain uveal melanomas acquire the capability to form blood channels that are not lined by endothelial cells (9 -11).Despite these intriguing observations extending over a halfcentury, very little is known about the presence of tumor cells in vessel walls, and whether some examples are an artifact of the methods used to identify such cells. Other clinically significant questions include: Are blood vessels whose lumen contains tumor cells perfused? Are they unusually leaky? Do the tumor cells actively participate in forming the wall structure? Do they traverse the vessel wall? Do the exposed tumor cells increase the frequency of metastasis? Are they more susceptible to immune attack? Here, we address two of these questions-frequency and perfusion-and examine the significance of mosaic vessels in human colon cancer as well as in corresponding animal models.To approach the problem, we first developed a technique by which cancer cells, endothelial cells, vessel morphology, and blood flow markers could be visualized simultaneously. To uniquely label cancer cells, we transfected the LS174T human colon adenocarcinoma cell line with a constitutively expressing green fluorescent protein (GFP) construct. The resulting fluorescent tumor cells then were implanted into mice and coul...

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Section: Discussionsupporting

confidence: 74%

Section: Discussionsupporting

confidence: 71%

Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood

Chang

Tomaso

McDonald

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

605

382

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show abstract

“…However, few studies have attempted to investigate the migration and localization of adoptively transferred activated lymphocytes or host leucocytes into the tumour environment or surrounding normal tissue using dynamic visualization techniques, such as in vivo microscopy (Sasaki et al, 1991;Fukumura et al, 1995;Melder et al, 1995). Thus, the mechanisms by which LAK cells and host immune cells are attracted to the tumour and then promote tumour necrosis remain unclear; however, several possibilities exist.…”

Section: Discussionmentioning

confidence: 99%

Leucocyte interactions with the mouse cremaster muscle microcirculation in vivo in response to tumour-conditioned medium

Brown

Reed²

1997

Br J Cancer

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Summary Leucocyte interactions with the cremaster muscle microcirculation in vivo were investigated in response to culture medium conditioned with different cell types in 25 adult male Swiss mice. Animals were divided into five groups. Three groups received ex vivo fluorescently labelled lymphokine activated killer (LAK) cells systemically and had either tumour (murine melanoma K1735)-conditioned medium (TCM), fibroblast (murine 3T3)-conditioned medium (FCM) or fresh culture medium administered topically to the cremaster muscle. In the two remaining groups, the host leucocytes were labelled fluorescently by systemic administration of acridine red, and either TCM or FCM was applied topically to the cremaster muscle. There was an immediate but transient increase in the frequency of rolling and adherent LAK cells, and a subsequent (90-120 min later) increase in rolling and adherent host leucocytes, demonstrating temporal differences in the response to topical administration of TCM. These increases in contact with the vascular endothelium occurred in all vessel types, venules, arterioles and capillaries, with the greatest response observed in the venules. The FCM and normal culture medium did not affect the distribution and localization of either LAK cells or host leucocytes. These data suggest that there are one or more soluble tumour-specific chemoattractants for leucocytes present in the conditioned medium. The mouse cremaster muscle microcirculation is therefore a useful model to investigate the mechanism of leucocyte-endothelium interactions in tumour biology.

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“…Using videomicroscopy, Jain's group (61)(62)(63) has defined this interrelationship elegantly, and they reported that neovessels are "sticky" and elicit rolling and stable arrest interactions with leukocytes. It now is established that neovessels at sites facilitate the recruitment of leukocytes, in part via distinct molecular receptor-ligand interactions, such as those that are mediated by adhesion molecules and chemokines (62,64,65).…”

Section: Development Of Angiogenesis In Immune Inflammationmentioning

confidence: 99%

Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection

Reinders

Rabelink

Briscoe

2006

Journal of the American Society of Nephrology

134

144

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Interaction of Activated Natural Killer Cells with Normal and Tumor Vessels in Cranial Windows in Mice

Cited by 38 publications

References 0 publications

Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood

Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood

Leucocyte interactions with the mouse cremaster muscle microcirculation in vivo in response to tumour-conditioned medium

Angiogenesis and Endothelial Cell Repair in Renal Disease and Allograft Rejection

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