A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth.
BACKGROUND: The stromal microenvironment and particularly the macrophage component of primary tumors influence their malignant potential. However, at the metastatic site the role of these cells and their mechanism of actions for establishment and growth of metastases remain largely unknown. METHODO...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2009
|
| _version_ | 1826257505805664256 |
|---|---|
| author | Qian, B Deng, Y Im, J Muschel, R Zou, Y Li, J Lang, R Pollard, J |
| author_facet | Qian, B Deng, Y Im, J Muschel, R Zou, Y Li, J Lang, R Pollard, J |
| author_sort | Qian, B |
| collection | OXFORD |
| description | BACKGROUND: The stromal microenvironment and particularly the macrophage component of primary tumors influence their malignant potential. However, at the metastatic site the role of these cells and their mechanism of actions for establishment and growth of metastases remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using animal models of breast cancer metastasis, we show that a population of host macrophages displaying a distinct phenotype is recruited to extravasating pulmonary metastatic cells regardless of species of origin. Ablation of this macrophage population through three independent means (genetic and chemical) showed that these macrophages are required for efficient metastatic seeding and growth. Importantly, even after metastatic growth is established, ablation of this macrophage population inhibited subsequent growth. Furthermore, imaging of intact lungs revealed that macrophages are required for efficient tumor cell extravasation. CONCLUSION/SIGNIFICANCE: These data indicate a direct enhancement of metastatic growth by macrophages through their effects on tumor cell extravasation, survival and subsequent growth and identifies these cells as a new therapeutic target for treatment of metastatic disease. |
| first_indexed | 2024-03-06T18:19:18Z |
| format | Journal article |
| id | oxford-uuid:05b8c843-53d1-4b27-8753-beb825cb9511 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:19:18Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:05b8c843-53d1-4b27-8753-beb825cb95112022-03-26T08:58:40ZA distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:05b8c843-53d1-4b27-8753-beb825cb9511EnglishSymplectic Elements at Oxford2009Qian, BDeng, YIm, JMuschel, RZou, YLi, JLang, RPollard, J BACKGROUND: The stromal microenvironment and particularly the macrophage component of primary tumors influence their malignant potential. However, at the metastatic site the role of these cells and their mechanism of actions for establishment and growth of metastases remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using animal models of breast cancer metastasis, we show that a population of host macrophages displaying a distinct phenotype is recruited to extravasating pulmonary metastatic cells regardless of species of origin. Ablation of this macrophage population through three independent means (genetic and chemical) showed that these macrophages are required for efficient metastatic seeding and growth. Importantly, even after metastatic growth is established, ablation of this macrophage population inhibited subsequent growth. Furthermore, imaging of intact lungs revealed that macrophages are required for efficient tumor cell extravasation. CONCLUSION/SIGNIFICANCE: These data indicate a direct enhancement of metastatic growth by macrophages through their effects on tumor cell extravasation, survival and subsequent growth and identifies these cells as a new therapeutic target for treatment of metastatic disease. |
| spellingShingle | Qian, B Deng, Y Im, J Muschel, R Zou, Y Li, J Lang, R Pollard, J A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. |
| title | A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. |
| title_full | A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. |
| title_fullStr | A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. |
| title_full_unstemmed | A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. |
| title_short | A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. |
| title_sort | distinct macrophage population mediates metastatic breast cancer cell extravasation establishment and growth |
| work_keys_str_mv | AT qianb adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT dengy adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT imj adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT muschelr adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT zouy adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT lij adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT langr adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT pollardj adistinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT qianb distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT dengy distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT imj distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT muschelr distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT zouy distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT lij distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT langr distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth AT pollardj distinctmacrophagepopulationmediatesmetastaticbreastcancercellextravasationestablishmentandgrowth |