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Early incorporated endothelial cells as origin of metastatic tumor vasculogenesis

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Abstract

Vascularization of solid tumors is thought to occur by sprouting or intussusceptive angiogenesis, co-option of existing vessels, and vasculogenic mimicry after the onset of tumor hypoxia, when the tumor radius exceeds the oxygen diffusion distance. In contrast, here we show that individual endothelial cells that are incorporated into pre-hypoxic tumors give rise to tumor blood vessels via vasculogenesis. Small metastatic lung tumor sections obtained after tail-vein injection of a syngeneic breast cancer cell line in the nude mice were labeled with antibodies against endothelial cell markers. Immunofluorescence showed the incorporation and mixed growth of CD31-, Tie-2-, and CD105-positive endothelial cells in tumors with radii less than oxygen diffusion distance and subsequent development of blood vessels from these early-incorporated endothelial cells. This observation lays the foundation of a novel vasculogenic paradigm of tumor vascularization, where incorporation of endothelial cells and their growth among tumor cells occur before the onset of core hypoxia in lung metastatic tumors.

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Acknowledgments

This work was supported by NIH P50 AT00428-01 Project 3 (ABA).

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Authors and Affiliations

  1. Department of Pharmacology and Center for Lung Biology, University of South Alabama, 307 N. University Blvd, MSB 3370, Mobile, AL, 36688, USA

    Khair Elzarrad, Abu Haroon, Darla Reed & Abu-Bakr Al-Mehdi

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  1. Khair Elzarrad
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  2. Abu Haroon
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  3. Darla Reed
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  4. Abu-Bakr Al-Mehdi
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Correspondence to Abu-Bakr Al-Mehdi.

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Authors’ contribution

MKE carried out the fluorescence imaging, immunofluorescence, experimental metastatic tumor development in the nude mice, and organized the data. ATH generated experimental metastatic tumors in the nude mice. DJR helped with cell culture and imaging. ABA conceived and designed the study and drafted the manuscript. All authors read and approved the manuscript.

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Elzarrad, K., Haroon, A., Reed, D. et al. Early incorporated endothelial cells as origin of metastatic tumor vasculogenesis. Clin Exp Metastasis 26, 589–598 (2009). https://doi.org/10.1007/s10585-009-9257-8

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  • DOI: https://doi.org/10.1007/s10585-009-9257-8

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