Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors

Laureen S. Ojalvo, Charles A. Whittaker, John S. Condeelis, Jeffrey W. Pollard

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

The tumor microenvironment modifies the malignancy of tumors. In solid tumors, this environment is populated by many macrophages that, in genetic studies that depleted these cells from mouse models of breast cancer, were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these tumor-promoting effects of macrophages are through the stimulation of tumor cell migration, invasion, intravasation, and enhancement of angiogenesis. Using an in vivo invasion assay, it was demonstrated that invasive carcinoma cells are a unique subpopulation of tumor cells whose invasion and chemotaxis is dependent on the comigration of tumor-associated macrophages (TAMs) with obligate reciprocal signaling through an epidermal growth factor-CSF-1 paracrine loop. In this study, these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison with TAMs isolated indiscriminately to function using established macrophage markers. Unsupervised analysis of transcript patterns showed that the invasion-associated TAMs represent a unique subpopulation of TAMs that, by gene ontology criteria, have gene expression patterns related to tissue and organ development. Gene set enrichment analysis showed that these macrophages are also specifically enriched for molecules involved in Wnt-signaling. Previously, it was shown that macrophage-derived Wnt molecules promote vascular remodeling and that tumor cells are highly motile and intravasate around perivascular TAM clusters. Taken together, we conjecture that invasive TAMs link angiogenesis and tumor invasion and that Wnt-signaling plays a role in mediating their activity.

Original languageEnglish (US)
Pages (from-to)702-712
Number of pages11
JournalJournal of Immunology
Volume184
Issue number2
DOIs
StatePublished - Jan 15 2010

Fingerprint

Macrophages
Breast Neoplasms
Gene Expression
Neoplasms
Gene Ontology
Macrophage Colony-Stimulating Factor
Tumor Microenvironment
Gene Expression Profiling
Chemotaxis
Epidermal Growth Factor
Cell Movement
Carcinoma

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. / Ojalvo, Laureen S.; Whittaker, Charles A.; Condeelis, John S.; Pollard, Jeffrey W.

In: Journal of Immunology, Vol. 184, No. 2, 15.01.2010, p. 702-712.

Research output: Contribution to journalArticle

@article{6ea5c2084f0d4699b7d205f408279bce,
title = "Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors",
abstract = "The tumor microenvironment modifies the malignancy of tumors. In solid tumors, this environment is populated by many macrophages that, in genetic studies that depleted these cells from mouse models of breast cancer, were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these tumor-promoting effects of macrophages are through the stimulation of tumor cell migration, invasion, intravasation, and enhancement of angiogenesis. Using an in vivo invasion assay, it was demonstrated that invasive carcinoma cells are a unique subpopulation of tumor cells whose invasion and chemotaxis is dependent on the comigration of tumor-associated macrophages (TAMs) with obligate reciprocal signaling through an epidermal growth factor-CSF-1 paracrine loop. In this study, these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison with TAMs isolated indiscriminately to function using established macrophage markers. Unsupervised analysis of transcript patterns showed that the invasion-associated TAMs represent a unique subpopulation of TAMs that, by gene ontology criteria, have gene expression patterns related to tissue and organ development. Gene set enrichment analysis showed that these macrophages are also specifically enriched for molecules involved in Wnt-signaling. Previously, it was shown that macrophage-derived Wnt molecules promote vascular remodeling and that tumor cells are highly motile and intravasate around perivascular TAM clusters. Taken together, we conjecture that invasive TAMs link angiogenesis and tumor invasion and that Wnt-signaling plays a role in mediating their activity.",
author = "Ojalvo, {Laureen S.} and Whittaker, {Charles A.} and Condeelis, {John S.} and Pollard, {Jeffrey W.}",
year = "2010",
month = "1",
day = "15",
doi = "10.4049/jimmunol.0902360",
language = "English (US)",
volume = "184",
pages = "702--712",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors

AU - Ojalvo, Laureen S.

AU - Whittaker, Charles A.

AU - Condeelis, John S.

AU - Pollard, Jeffrey W.

PY - 2010/1/15

Y1 - 2010/1/15

N2 - The tumor microenvironment modifies the malignancy of tumors. In solid tumors, this environment is populated by many macrophages that, in genetic studies that depleted these cells from mouse models of breast cancer, were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these tumor-promoting effects of macrophages are through the stimulation of tumor cell migration, invasion, intravasation, and enhancement of angiogenesis. Using an in vivo invasion assay, it was demonstrated that invasive carcinoma cells are a unique subpopulation of tumor cells whose invasion and chemotaxis is dependent on the comigration of tumor-associated macrophages (TAMs) with obligate reciprocal signaling through an epidermal growth factor-CSF-1 paracrine loop. In this study, these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison with TAMs isolated indiscriminately to function using established macrophage markers. Unsupervised analysis of transcript patterns showed that the invasion-associated TAMs represent a unique subpopulation of TAMs that, by gene ontology criteria, have gene expression patterns related to tissue and organ development. Gene set enrichment analysis showed that these macrophages are also specifically enriched for molecules involved in Wnt-signaling. Previously, it was shown that macrophage-derived Wnt molecules promote vascular remodeling and that tumor cells are highly motile and intravasate around perivascular TAM clusters. Taken together, we conjecture that invasive TAMs link angiogenesis and tumor invasion and that Wnt-signaling plays a role in mediating their activity.

AB - The tumor microenvironment modifies the malignancy of tumors. In solid tumors, this environment is populated by many macrophages that, in genetic studies that depleted these cells from mouse models of breast cancer, were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these tumor-promoting effects of macrophages are through the stimulation of tumor cell migration, invasion, intravasation, and enhancement of angiogenesis. Using an in vivo invasion assay, it was demonstrated that invasive carcinoma cells are a unique subpopulation of tumor cells whose invasion and chemotaxis is dependent on the comigration of tumor-associated macrophages (TAMs) with obligate reciprocal signaling through an epidermal growth factor-CSF-1 paracrine loop. In this study, these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison with TAMs isolated indiscriminately to function using established macrophage markers. Unsupervised analysis of transcript patterns showed that the invasion-associated TAMs represent a unique subpopulation of TAMs that, by gene ontology criteria, have gene expression patterns related to tissue and organ development. Gene set enrichment analysis showed that these macrophages are also specifically enriched for molecules involved in Wnt-signaling. Previously, it was shown that macrophage-derived Wnt molecules promote vascular remodeling and that tumor cells are highly motile and intravasate around perivascular TAM clusters. Taken together, we conjecture that invasive TAMs link angiogenesis and tumor invasion and that Wnt-signaling plays a role in mediating their activity.

UR - http://www.scopus.com/inward/record.url?scp=76249106734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76249106734&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0902360

DO - 10.4049/jimmunol.0902360

M3 - Article

C2 - 20018620

AN - SCOPUS:76249106734

VL - 184

SP - 702

EP - 712

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -