Endosialin/TEM 1/CD248 is a pericyte marker of embryonic and tumor neovascularization

Bagley, Rebecca G.; Honma, Nakayuki; Weber, William; Boutin, Paula; Rouleau, Cecile; Shankara, Srinivas; Kataoka, Satoshi; Ishida, Isao; Roberts, Bruce; Teicher, Beverly A.

doi:10.1016/j.mvr.2008.07.008

Cited by 86 publications

(92 citation statements)

References 36 publications

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“…The tubes/networks that MSC can establish may provide structural support in vivo as stroma or could potentially serve as a framework for vascular development during periods of active angiogenesis. Anti-endosialin was also effective at preventing tube/network formation by pericytes and endothelial precursor cells indicating that targeting endosialin can influence multiple cell types which contribute to tumor growth associated with vasculature and stroma (40,41).…”

Section: Discussionmentioning

confidence: 99%

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Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

Weber¹,

Rouleau²,

Yang³

et al. 2009

Int J Oncol

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Abstract. Tumor development is a complex and dynamic process that involves malignant, vascular, and stromal cells. Endosialin is a tumor endothelial marker (TEM) present in the microvasculature and stroma of human tumors. Cancerassociated fibroblasts (CAF) have been implicated in promoting tumor development and have been associated with mesenchymal stem cells (MSC). Since stem/progenitor cells recruited either from bone marrow or residing in nearby tissues can contribute to pathological processes we investigated endosialin in MSC using a novel monoclonal antibody. Endosialin is highly expressed by CAF and human bone marrow-derived MSC. MSC can form networks in a tube formation assay that is inhibited by an anti-endosialin antibody. Immunohistochemistry for human endosialin in xenograft tumors following co-injection of MSC and cancer cells identified MSC in tumor stroma. MSC are a potential target for anticancer therapeutic intervention and endosialin expression offers a new tool for the identification of MSC. Endosialin expression by both CAF and MSC further implies the potential contribution of MSC to tumor stroma via differentiation into tumor stromal fibroblasts.

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Section: Discussionmentioning

confidence: 99%

“…Although endosialin was described to be a tumor endothelial marker implying selective endothelial cell expression for endosialin, expression of endosialin has been documented in other cell types (11). Endosialin has been detected in fibroblasts, perivascular in the tumor microenvironment and mesenchymal malignant cells (14,16,21,41,46).…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

Weber¹,

Rouleau²,

Yang³

et al. 2009

Int J Oncol

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show abstract

“…15 Subsequently, TEM-1/collagen IV co-localization was confirmed by confocal microscopy. 10 Other studies have demonstrated the importance of TEM-1 in regulating proliferation, 12 tube formation on matrigel, 11,16 and cell migration. 11,12 However, the exact mechanism(s)…”

Section: Introductionmentioning

confidence: 99%

Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Tomkowicz

Rybiński²,

Sebeck³

et al. 2010

Cancer Biology & Therapy

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“…Thus, to exploit both passive and active targeting potentials, we engineered SHK-loaded PEGylated PLGA NPs decorated with anti-TEM1 Ab/scFv. TEM1 has been reported to be expressed by the endothelial cells of ovarian tumor vasculature 25,[44][45][46][47] and other malignancies such as brain and abdominal tumors. 48,49 Based on the release profile, less than 20% of drug can be released within 2 hours, during which the engineered NPs can safely pass the blood stream and reach the target site with negligible inadvertent detrimental impacts on blood-circulating immune system cells.…”

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confidence: 99%

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

Barar

Sandaltzopoulos

Liu

et al. 2014

IJN

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Conventional chemotherapy of ovarian cancer often fails because of initiation of drug resistance and/or side effects and trace of untouched remaining cancerous cells. This highlights an urgent need for advanced targeted therapies for effective remediation of the disease using a cytotoxic agent with immunomodulatory effects, such as shikonin (SHK). Based on preliminary experiments, we found SHK to be profoundly toxic in ovarian epithelial cancer cells (OVCAR-5 and ID8 cells) as well as in normal ovarian IOSE-398 cells, endothelial MS1 cells, and lymphocytes. To limit its cytotoxic impact solely to tumor cells within the tumor microenvironment (TME), we aimed to engineer SHK as polymeric nanoparticles (NPs) with targeting moiety toward tumor microvasculature. To this end, using single/double emulsion solvent evaporation/diffusion technique with sonication, we formulated biodegradable NPs of poly(lactic-co-glycolic acid) (PLGA) loaded with SHK. The surface of NPs was further decorated with solubilizing agent polyethylene glycol (PEG) and tumor endothelial marker 1 (TEM1)/endosialin-targeting antibody (Ab) through carbodiimide/N-hydroxysuccinimide chemistry. Having characterized the physicochemical and morphological properties of NPs, we studied their drug-release profiles using various kinetic models. The biological impact of NPs was also evaluated in tumor-associated endothelial MS1 cells, primary lymphocytes, and epithelial ovarian cancer OVCAR-5 cells. Based on particle size analysis and electron microscopy, the engineered NPs showed a smooth spherical shape with size range of 120 to 250 nm and zeta potential value of −30 to −40 mV. Drug entrapment efficiency was ~80%–90%, which was reduced to ~50%–60% upon surface decoration with PEG and Ab. The liberation of SHK from NPs showed a sustained-release profile that was best fitted with Wagner log-probability model. Fluorescence microscopy and flow cytometry analysis showed active interaction of Ab-armed NPs with TEM1-positive MS1 cells, but not with TEM1-negative MS1 cells. While exposure of the PEGylated NPs for 2 hours was not toxic to lymphocytes, long-term exposure of the Ab-armed and PEGylated NPs was significantly toxic to TEM1-positive MS1 cells and OVCAR-5 cells. Based on these findings, we propose SHK-loaded Ab-armed PEGylated PLGA NPs as a novel nanomedicine for targeted therapy of solid tumors.

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Endosialin/TEM 1/CD248 is a pericyte marker of embryonic and tumor neovascularization

Cited by 86 publications

References 36 publications

Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers

Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signaling

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

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