Physical Biology in Cancer. 3. The role of cell glycocalyx in vascular transport of circulating tumor cells

Mitchell, Michael J.; King, Michael R.

doi:10.1152/ajpcell.00285.2013

Cited by 80 publications

(72 citation statements)

References 132 publications

(175 reference statements)

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“…Cell surface glycoproteins. As mentioned previously, tumor cells have been associated with the overexpression of cell surface glycoproteins, such as chondroitin sulfate and hyaluronic acid Itano and Kimata, 2008;Mitchell and King, 2014). Moreover, glycoproteins expressed on the surface of tumor cells usually contain carbohydrate moieties that are different from those found on normal cells (Bies et al, 2004).…”

Section: B Active Targetingmentioning

confidence: 99%

“…It is believed that the inside surface of blood vessels, as well as the surface of endothelial cells, contain many negatively charged components (Davis et al, 2008). This is because vascular endothelial cells often express a sugar-rich protein coating called the glycocalyx (van Golen et al, 2012;Mitchell and King, 2014). Structurally, the glycocalyx is a network of mostly membrane-bound proteoglycans and some glycoproteins (Fuster and Esko, 2005;Reitsma et al, 2007).…”

Section: Surface Chargementioning

confidence: 99%

“…Similarly, cancer cells and tumor endothelial cells have also been associated with the overexpression of glycosaminoglycans, including heparin sulfate, chondroitin sulfate, and hyaluronic acid (Vijayagopal et al, 1998;Park et al, 2002;Davies et al, 2004;Abid et al, 2006;Fears et al, 2006). This may influence the distribution of nanoparticles and the uptake of nanoparticles by these cells (Campbell et al, 2002;Lee et al, 2002;Itano and Kimata, 2008;Mitchell and King, 2014).…”

Section: Surface Chargementioning

confidence: 99%

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Section: B Active Targetingmentioning

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Section: Surface Chargementioning

confidence: 99%

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“…For intravasation, the tumor cell must invade through the tumor stroma (Chiang & Massague, 2008; Joyce & Pollard, 2009). HA, such as that found in the HA-rich stroma of tumors, can induce expression of several ECM degrading enzymes on tumor cells including the matrix metalloproteinases MT1-MMP, MMP-2, MMP-7, and MMP-9 as well as EMMPRIN and the cysteine proteases cathepsin D and cathepsin K (Abecassis, Olofsson, Schmid, Zalcman, & Karniguian, 2003; Bourguignon et al, 2004; Chetty et al, 2012; Droller, 2003; Kim et al, 2008; Kosunen et al, 2007; Marrero-Diaz et al, 2009; Mitchell & King, 2014; Murray, Morrin, & McDonnell, 2004; Nalla, Gorantla, Gondi, Lakka, & Rao, 2010; Veeravalli et al, 2010). Once at the blood vessel, the tumor cell can secrete a host of factors to induce disruption of EC junctions and EC retraction including MMP1, ADAM12, and TNF1α to allow for paracellular transendothelial migration (Mierke, 2011).…”

Section: Ha Regulation Of Endothelial Barrier Function During Cancmentioning

confidence: 99%

Hyaluronan Regulation of Endothelial Barrier Function in Cancer

Singleton

2014

Advances in Cancer Research

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Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated by endothelial cell–cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including tumor angiogenesis and metastasis. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through specific mechanisms including HA-binding protein signaling in caveolin-enriched microdomains, a subset of lipid rafts. Certain disease states, including cancer, increase enzymatic hyaluronidase activity and reactive oxygen species generation, which break down high molecular weight HA (HMW-HA) to low molecular weight fragments (LMW-HA). LMW-HA can activate specific HA-binding proteins during tumor progression to promote disruption of endothelial cell–cell contacts. In contrast, exogenous administration of HMW-HA promotes enhancement of vascular integrity. This review focuses on the roles of HA in regulating angiogenic and metastatic processes based on its size and the HA-binding proteins present. Further, potential therapeutic applications of HMW-HA in treating cancer are discussed.

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“…To investigate tumor cell adhesion in the microcirculation (11,21), microfluidic flow assays were utilized to simulate CTC-EC interactions by quantifying rolling velocity and displacement of the cell line aggregates on E-selectin coated surfaces. The selectin-mediated capture of leukocytes (e.g., neutrophils) from flowing blood has been extensively studied in flow systems of various designs (24).…”

Section: Discussionmentioning

confidence: 99%

A physical sciences network characterization of circulating tumor cell aggregate transport

King

Phillips

Mitrugno

et al. 2015

American Journal of Physiology-Cell Physiology

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Circulating tumor cells (CTC) have been implicated in the hematogenous spread of cancer. To investigate the fluid phase of cancer from a physical sciences perspective, the multi-institutional Physical Sciences-Oncology Center (PS-OC) Network performed multidisciplinary biophysical studies of single CTC and CTC aggregates from a patient with breast cancer. CTCs, ranging from single cells to aggregates comprised of 2-5 cells, were isolated using the high-definition CTC assay and biophysically profiled using quantitative phase microscopy. Single CTCs and aggregates were then modeled in an in vitro system comprised of multiple breast cancer cell lines and microfluidic devices used to model E-selectin mediated rolling in the vasculature. Using a numerical model coupling elastic collisions between red blood cells and CTCs, the dependence of CTC vascular margination on single CTCs and CTC aggregate morphology and stiffness was interrogated. These results provide a multifaceted characterization of single CTC and CTC aggregate dynamics in the vasculature and illustrate a framework to integrate clinical, biophysical, and mathematical approaches to enhance our understanding of the fluid phase of cancer.circulating tumor cell; metastasis; breast cancer; cell lines; fluid dynamics; physics of cancer; hemodynamics; quantitative phase microscopy; microfluidics; immersed finite element method WHILE THE PRESENCE of circulating tumor cells (CTCs) in the vasculature has been implicated in the metastatic cascade of epithelial carcinomas, new evidence has revealed a putative role of CTC aggregates as a potential form of stromal-assisted metastasis across a variety of epithelial tumor types (6). In concert, the presence of homotypic interactions among CTCs leading to aggregation occurring at sites of endothelial attachment suggest the involvement of CTC aggregates in the hematogenous dissemination of cancer. Despite compelling evidence suggesting a role for CTC aggregates in metastatic progression (28), the physics underlying CTC vascular transport including the influence of blood flow, coagulation, intercellular adhesion, and collisions with cells of the vasculature, such as red blood cells (RBCs) and endothelial cells (ECs), remains poorly understood. Better physical understanding of CTC transport and mechanobiology could enable, for example, new strategies to monitor patient response to chemotherapy (22).Here, we demonstrate a multidisciplinary approach (29) that utilizes clinical measurements on single CTCs and CTC aggregates from a patient with breast cancer as a quantitative guide in the rational design of in vitro and in silico models to investigate the dynamics of CTC transport in the vasculature. Using the high-definition (HD) CTC assay to identify circulating tumor cells in the blood, coupled with quantitative phase microscopy (QPM) to quantify the subcellular density organization of CTCs, we profiled the biophysical properties of CTCs in a patient with breast cancer. These metrics, including geometric and density features,...

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Physical Biology in Cancer. 3. The role of cell glycocalyx in vascular transport of circulating tumor cells

Cited by 80 publications

References 132 publications

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

Hyaluronan Regulation of Endothelial Barrier Function in Cancer

A physical sciences network characterization of circulating tumor cell aggregate transport

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