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Mouse Breast Carcinoma Monocytic/Macrophagic Myeloid-Derived Suppressor Cell Infiltration as a Consequence of Endothelial Dysfunction in Shb-Deficient Endothelial Cells Increases Tumor Lung Metastasis
- Source :
- International Journal of Molecular Sciences, Vol 22, Iss 11478, p 11478 (2021), International Journal of Molecular Sciences, Volume 22, Issue 21
- Publication Year :
- 2021
- Publisher :
- Uppsala universitet, Institutionen för medicinsk cellbiologi, 2021.
-
Abstract
- Metastasis reflects both the inherent properties of tumor cells and the response of the stroma to the presence of the tumor. Vascular barrier properties, either due to endothelial cell (EC) or pericyte function, play an important role in metastasis in addition to the contribution of the immune system. The Shb gene encodes the Src homology-2 domain protein B that operates downstream of tyrosine kinases in both vascular and immune cells. We have investigated E0771.lmb breast carcinoma metastasis in mice with conditional deletion of the Shb gene using the Cdh5-CreERt2 transgene, resulting in inactivation of the Shb-gene in EC and some hematopoietic cell populations. Lung metastasis from orthotopic tumors, tumor vascular and immune cell characteristics, and immune cell gene expression profiles were determined. We found no increase in vascular leakage that could explain the observed increase in metastasis upon the loss of Shb expression. Instead, Shb deficiency in EC promoted the recruitment of monocytic/macrophagic myeloid-derived suppressor cells (mMDSC), an immune cell type that confers a suppressive immune response, thus enhancing lung metastasis. An MDSC-promoting cytokine/chemokine profile was simultaneously observed in tumors grown in mice with EC-specific Shb deficiency, providing an explanation for the expanded mMDSC population. The results demonstrate an intricate interplay between tumor EC and immune cells that pivots between pro-tumoral and anti-tumoral properties, depending on relevant genetic and/or environmental factors operating in the microenvironment.
- Subjects :
- SHB
Lung Neoplasms
Angiogenesis
medicine.medical_treatment
Cell- och molekylärbiologi
Cell
Monocytes
Metastasis
Mice
angiogenesis
Tumor Microenvironment
breast carcinoma
Biology (General)
Spectroscopy
Uncategorized
Mice, Knockout
Neovascularization, Pathologic
General Medicine
Cadherins
Computer Science Applications
Endothelial stem cell
Chemistry
medicine.anatomical_structure
Cytokine
Female
Pericyte
QH301-705.5
Mammary Neoplasms, Animal
Biology
Catalysis
Article
Inorganic Chemistry
Immune system
Antigens, CD
Proto-Oncogene Proteins
medicine
Animals
metastasis
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
Cancer och onkologi
Macrophages
Myeloid-Derived Suppressor Cells
Organic Chemistry
Endothelial Cells
medicine.disease
Mice, Inbred C57BL
Cancer and Oncology
Cancer research
Myeloid-derived Suppressor Cell
immune suppression
Cell and Molecular Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences, Vol 22, Iss 11478, p 11478 (2021), International Journal of Molecular Sciences, Volume 22, Issue 21
- Accession number :
- edsair.doi.dedup.....5604ec11f0d12b387ea715944b6cd482