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Hematopoietic Derived Cell Infiltration of the Intestinal Tumor Microenvironment in ApcMin/+ Mice

Published online by Cambridge University Press:  08 April 2011

Celestia Davis ,
Robert Price ,
Grishma Acharya ,
Troy Baudino ,
Thomas Borg ,
Franklin G. Berger  and
Maria Marjorette O. Peña
Celestia Davis
Affiliation:
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
Robert Price
Affiliation:
Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA Department of Cell and Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
Grishma Acharya
Affiliation:
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA
Troy Baudino
Affiliation:
Department of Cell and Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
Thomas Borg
Affiliation:
Department of Cell and Developmental Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
Franklin G. Berger
Affiliation:
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA
Maria Marjorette O. Peña*
Affiliation:
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA Center for Colon Cancer Research, University of South Carolina, Columbia, SC 29208, USA
*
Corresponding author. E-mail: mpena@biol.sc.edu
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Abstract

Tumors consist of a heterogeneous population of neoplastic cells infiltrated by an equally heterogeneous collection of nonneoplastic cells that comprise the tumor microenvironment. Tumor growth, invasion, and metastasis depend on multiple interactions between these cells. To assess their potential as therapeutic targets or vehicles for tumor specific delivery of therapeutic agents, we examined the contribution of bone marrow derived cells (BMDCs) to the intestinal tumor microenvironment. Hematopoietic stem cells expressing the enhanced green fluorescent protein (eGFP) were transplanted into lethally irradiated ApcMin/+ mice, and their engraftment was analyzed by confocal microscopy. The results showed abundant infiltration of eGFP cells into the small intestine, colon, and spleen compared to heart, muscle, liver, lung, and kidney. Within the intestine, there was a pronounced gradient of engraftment along the anterior to posterior axis, with enhanced infiltration into adenomas. Immunofluorescence analysis showed that osteopontin was expressed in tumor stromal cells but not in nontumor stromal populations, suggesting that gene expression in these cells is distinct. Tumor vasculature in ApcMin/+ mice was chaotic compared to normal intestinal regions. Our data suggest that BMDCs can be harnessed for tumor-targeted therapies to enhance antitumor efficacy.

Keywords

tumor microenvironmenthematopoietic stem cellsbone marrow derived cellscolon cancerApcMin/+ mice
Type
Cover Article
Information
Microscopy and Microanalysis , Volume 17 , Issue 4 , August 2011 , pp. 528 - 539
Copyright
Copyright © Microscopy Society of America 2011

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