Biomedical subjects

G C Koenig

Publications and source records attributed to G C Koenig.

5 recordsLinked to original sources

PubMed2000

Local imbalance of proangiogenic and antiangiogenic factors: a potential mechanism of focal necrosis and dormancy in tumors.

Solid tumors produce both stimulators and inhibitors of angiogenesis. The suppression of metastases by some primary tumors has been attributed to the longer circulatory half-lives of the inhibitors. We propose that intrinsic differences in the physicochemical properties of these regulators may also explain focal suppression of angiogenesis within the primary tumor. We present a mathematical framework that describes production, diffusion, and degradation of these factors in tumor and host tissue and their effect on angiogenesis at local and distal sites. Results show focal suppression of angiogenesis, provide an explanation for tumor dormancy and focal necrosis, and predict a suppressive influence of primary tumors on angiogenesis at metastatic sites. They suggest generally that diffusible factors produced by tumors can stimulate responses in adjacent host tissue, preparing it for further tumor invasion. This study presents a new paradigm for the development of tumor necrosis and offers new insight into angiogenesis regulation and therapy. The framework established for modeling the competing effects of diffusible stimulators and inhibitors can be applied more generally to growth factors/inhibitors and other opposing factors produced in the tumor environment.

Angiogenesis Inducing Agents↗

PubMed1996

Leukocyte-endothelial adhesion and angiogenesis in tumors.

Leukocyte-endothelial adhesion and angiogenesis, until recently considered as separate processes, have been shown to be linked by two recent findings: soluble cellular adhesion molecules (CAMs) involved in leukocyte-endothelial interactions are angiogenic and well known angiogenic molecules secreted by cancer or immune. cells can modulate the endothelial CAMs. This molecular link may partially explain why the overall leukocyte-endothelial interaction is often low and heterogeneous in angiogenic tumor vessels and why activated lymphocytes adhere nonuniformly to tumor vessels when injected into the tumor's blood supply.

Animals↗

PubMed1996

During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium.

Localization of activated natural killer (A-NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell-adhesion molecules ICAM-1 and VCAM-1 on the tumor endothelium, mediated by lymphocyte function-associated protein LFA-1 and vascular lymphocyte function-associated protein VLA-4. In vitro and in vivo studies of A-NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes.

Animals↗

PubMed1995

Kinetics of adhesion molecule expression and spatial organization using targeted sampling fluorometry.

Cellular interactions with the vascular wall under flow conditions are controlled, in part, by the density of adhesion molecules on endothelial cells. The spatial arrangement and absolute levels of these molecules over the endothelium are therefore important determinants of cellular localization. Many biochemical and functional studies have characterized the interactions between leukocytes and endothelial monolayers, but no reliable method has been reported for quantifying the spatial expression of adhesion molecules on intact endothelial cell monolayers. We report the development of targeted sampling fluorometry (TSF), which uses standard immunostaining, fluorescence microscopy and digital image analysis techniques to analyze cell surface molecule expression on a cell-by-cell basis. This technique is performed on an intact monolayer and results in cellular intensity distributions that reflect spatial heterogeneity in adhesion molecule expression. We demonstrate the use of targeted sampling fluorometry in a study of the kinetics of tumor necrosis factor alpha-induced activation of human umbilical vein endothelial cell monolayers and show that the spatial patterns of adhesion molecule expression correlate with the locations of bound lymphocytes.

Cell Adhesion Molecules↗

PubMedDate not supplied

Adhesion of activated natural killer cells to tumor necrosis factor-alpha-treated endothelium under physiological flow conditions.

Adhesion of activated natural killer (A-NK) cells to activated and nonactivated endothelial cells in vitro was studied under dynamic flow conditions. Endothelial cells grown on glass slides were either treated with tumor necrosis factor-alpha (TNF alpha) or medium, then placed into a flow chamber over which suspensions of A-NK cells were passed using a range of defined shear stress levels. Significant numbers of binding cells could be consistently observed at shear stress levels less than 3 dyn/cm2 on TNF alpha-activated endothelium or at 0.59 dyn/cm2 on nonactivated endothelium. Stable adhesion occurred rapidly following the initial interaction of the following cells with the endothelium in the absence of detectable rolling. Pretreatment of the A-NK cells with monoclonal antibodies directed against CD18 (LFA-1) or CD49d (VLA-4) resulted in a significant reduction in the number of binding cells. Simultaneous treatment with both monoclonal antibodies eliminated all A-NK adhesion occurring over 0.5 dyn/cm2. Pretreatment of the endothelial cells with antibodies against E- or P-selectin resulted in a small but significant reduction in binding only at 0.5 dyn/cm2. The binding efficiency of the A-NK cells was similar to that previously observed for T lymphocytes under the same conditions. Once bound, approximately half of the adherent cells could resist detachment when exposed to wall shear stresses over 12 dyn/cm2. These findings indicate that A-NK cell adhesion to activated endothelium can occur under shear stress conditions which are representative of postcapillary venules and that this binding is mediated principally by both CD18 and CD49d. A-NK cell adhesion also occurs to nonactivated endothelium but only at wall shear stress levels less than 1 dyn/cm2.

Cell Adhesion↗