Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling
Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out t...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-06-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/9/6/68 |
| _version_ | 1797723217173938176 |
|---|---|
| author | Amy R. Dwyer Eloise L. Greenland Fiona J. Pixley |
| author_facet | Amy R. Dwyer Eloise L. Greenland Fiona J. Pixley |
| author_sort | Amy R. Dwyer |
| collection | DOAJ |
| description | Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out their various roles. In cancers, the macrophage’s interstitial migratory ability is frequently co-opted by tumor cells to enable escape from the primary tumor and metastatic spread. Macrophage accumulation within and movement through a tumor is often stimulated by tumor cell production of the mononuclear phagocytic growth factor, colony-stimulating factor-1 (CSF-1). CSF-1 also regulates macrophage survival, proliferation and differentiation, and its many effects are transduced by its receptor, the CSF-1R, via phosphotyrosine motif-activated signals. Mutational analysis of CSF-1R signaling indicates that the major mediators of CSF-1-induced motility are phosphatidyl-inositol-3 kinase (PI3K) and one or more Src family kinase (SFK), which activate signals to adhesion, actin polymerization, polarization and, ultimately, migration and invasion in macrophages. The macrophage transcriptome, including that of the motility machinery, is very complex and highly responsive to the environment, with selective expression of proteins and splice variants rarely found in other cell types. Thus, their unique motility machinery can be specifically targeted to block macrophage migration, and thereby, inhibit tumor invasion and metastasis. |
| first_indexed | 2024-03-12T09:59:42Z |
| format | Article |
| id | doaj.art-c3389a2603474ec3aed93ba769cc5db6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T09:59:42Z |
| publishDate | 2017-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c3389a2603474ec3aed93ba769cc5db62023-09-02T11:54:13ZengMDPI AGCancers2072-66942017-06-01966810.3390/cancers9060068cancers9060068Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility SignalingAmy R. Dwyer0Eloise L. Greenland1Fiona J. Pixley2School of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, AustraliaSchool of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, AustraliaSchool of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, AustraliaMacrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out their various roles. In cancers, the macrophage’s interstitial migratory ability is frequently co-opted by tumor cells to enable escape from the primary tumor and metastatic spread. Macrophage accumulation within and movement through a tumor is often stimulated by tumor cell production of the mononuclear phagocytic growth factor, colony-stimulating factor-1 (CSF-1). CSF-1 also regulates macrophage survival, proliferation and differentiation, and its many effects are transduced by its receptor, the CSF-1R, via phosphotyrosine motif-activated signals. Mutational analysis of CSF-1R signaling indicates that the major mediators of CSF-1-induced motility are phosphatidyl-inositol-3 kinase (PI3K) and one or more Src family kinase (SFK), which activate signals to adhesion, actin polymerization, polarization and, ultimately, migration and invasion in macrophages. The macrophage transcriptome, including that of the motility machinery, is very complex and highly responsive to the environment, with selective expression of proteins and splice variants rarely found in other cell types. Thus, their unique motility machinery can be specifically targeted to block macrophage migration, and thereby, inhibit tumor invasion and metastasis.http://www.mdpi.com/2072-6694/9/6/68macrophage motilitycolony-stimulating factor-1phosphatidyl-inositol-3-kinaseSrc family kinasesparacrine interaction |
| spellingShingle | Amy R. Dwyer Eloise L. Greenland Fiona J. Pixley Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling Cancers macrophage motility colony-stimulating factor-1 phosphatidyl-inositol-3-kinase Src family kinases paracrine interaction |
| title | Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling |
| title_full | Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling |
| title_fullStr | Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling |
| title_full_unstemmed | Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling |
| title_short | Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling |
| title_sort | promotion of tumor invasion by tumor associated macrophages the role of csf 1 activated phosphatidylinositol 3 kinase and src family kinase motility signaling |
| topic | macrophage motility colony-stimulating factor-1 phosphatidyl-inositol-3-kinase Src family kinases paracrine interaction |
| url | http://www.mdpi.com/2072-6694/9/6/68 |
| work_keys_str_mv | AT amyrdwyer promotionoftumorinvasionbytumorassociatedmacrophagestheroleofcsf1activatedphosphatidylinositol3kinaseandsrcfamilykinasemotilitysignaling AT eloiselgreenland promotionoftumorinvasionbytumorassociatedmacrophagestheroleofcsf1activatedphosphatidylinositol3kinaseandsrcfamilykinasemotilitysignaling AT fionajpixley promotionoftumorinvasionbytumorassociatedmacrophagestheroleofcsf1activatedphosphatidylinositol3kinaseandsrcfamilykinasemotilitysignaling |