Components of the hematopoietic compartments in tumor stroma and tumor-bearing mice

HoangDinh Huynh; Junke Zheng; Masato Umikawa; Robert Silvany; Xian-Jin Xie; Catherine J Wu; Martin Holzenberger; Qianming Wang; Cheng Cheng Zhang

doi:10.1371/journal.pone.0018054

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Components of the hematopoietic compartments in tumor stroma and tumor-bearing mice

Journal article

Open access

Peer reviewed

Components of the hematopoietic compartments in tumor stroma and tumor-bearing mice

HoangDinh Huynh, Junke Zheng, Masato Umikawa, Robert Silvany, Xian-Jin Xie, Catherine J Wu, Martin Holzenberger, Qianming Wang and Cheng Cheng Zhang

PloS one, Vol.6(3), e18054

03/25/2011

DOI: 10.1371/journal.pone.0018054

PMCID: PMC3064668

PMID: 21464968

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Abstract

Solid tumors are composed of cancerous cells and non-cancerous stroma. A better understanding of the tumor stroma could lead to new therapeutic applications. However, the exact compositions and functions of the tumor stroma are still largely unknown. Here, using a Lewis lung carcinoma implantation mouse model, we examined the hematopoietic compartments in tumor stroma and tumor-bearing mice. Different lineages of differentiated hematopoietic cells existed in tumor stroma with the percentage of myeloid cells increasing and the percentage of lymphoid and erythroid cells decreasing over time. Using bone marrow reconstitution analysis, we showed that the tumor stroma also contained functional hematopoietic stem cells. All hematopoietic cells in the tumor stroma originated from bone marrow. In the bone marrow and peripheral blood of tumor-bearing mice, myeloid populations increased and lymphoid and erythroid populations decreased and numbers of hematopoietic stem cells markedly increased with time. To investigate the function of hematopoietic cells in tumor stroma, we co-implanted various types of hematopoietic cells with cancer cells. We found that total hematopoietic cells in the tumor stroma promoted tumor development. Furthermore, the growth of the primary implanted Lewis lung carcinomas and their metastasis were significantly decreased in mice reconstituted with IGF type I receptor-deficient hematopoietic stem cells, indicating that IGF signaling in the hematopoietic tumor stroma supports tumor outgrowth. These results reveal that hematopoietic cells in the tumor stroma regulate tumor development and that tumor progression significantly alters the host hematopoietic compartment.

Cell Differentiation

Cell Compartmentation

Animals

Cell Proliferation

Stromal Cells - pathology

Cell Count

Hematopoietic Stem Cell Transplantation

Hematopoietic Stem Cells - pathology

Precancerous Conditions - pathology

Mice

Neoplasms - pathology

Details

Title: Subtitle: Components of the hematopoietic compartments in tumor stroma and tumor-bearing mice
Creators: HoangDinh Huynh - Department of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
Junke Zheng
Masato Umikawa
Robert Silvany
Xian-Jin Xie
Catherine J Wu
Martin Holzenberger
Qianming Wang
Cheng Cheng Zhang
Resource Type: Journal article
Publication Details: PloS one, Vol.6(3), e18054
DOI: 10.1371/journal.pone.0018054
PMID: 21464968
PMCID: PMC3064668
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: United States
Grant note: K01 CA120099 / NCI NIH HHS PR093256 / OCPHP CDC HHS K01CA120099 / NCI NIH HHS
Language: English
Date published: 03/25/2011
Academic Unit: Preventive and Community Dentistry; Biostatistics; Dental Research
Record Identifier: 9983917786802771

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