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In vivo two-photon characterization of tumor-associated macrophages and microglia (TAM/M) and CX3CR1 during different steps of brain metastasis formation from lung cancer
- Source :
- Neoplasia (New York, N.Y.), Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 11, Pp 1089-1100 (2021)
- Publication Year :
- 2021
-
Abstract
- Brain metastases frequently occur in lung cancer and dramatically limit prognosis of affected patients. The influence of tumor-associated macrophages and microglia (TAM/M) and their receptor CX3CR1 on different steps of brain metastasis formation from lung cancer is poorly characterized. We established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intravital 2-photon laser scanning microscopy. This allowed in vivo tracking of fluorescence-expressing tumor cells and TAM/M on a single-cell level over weeks. Intracarotid injection of red tdTomato-fluorescent Lewis lung carcinoma cell was performed in transgenic mice either proficient or deficient for CX3CR1. After intracarotid cell injection, intravascular tumor cells extravasated into the brain parenchyma and formed micro- and mature macrometastases. We observed potential phagocytosis of extravasated tumor cells by TAM/M. However, during later steps of metastasis formation, these anti-tumor effects diminished and were paralleled by TAM/M accumulation and activation. Although CX3CR1 deficiency resulted in a lower number of extravasated tumor cells, progression of these extravasated cells into micro metastases was more efficient. Overall, this resulted in a comparable number of mature macrometastases in CX3CR1-deficient and -proficient mice. Our findings indicate that unspecific inhibition of CX3CR1 might not be a suitable therapeutic option to prevent dissemination of lung cancer cells to the brain. Given the close interaction between TAM/M and tumor cells during metastasis formation, other therapeutic approaches targeting TAM/M function may warrant further evaluation. The herein established orthotopic mouse model may be a useful tool to evaluate such concepts in vivo.
- Subjects :
- Genetically modified mouse
Cancer Research
Lung Neoplasms
Cell
CX3C Chemokine Receptor 1
microglia
Mice
CX3CR1
Phagocytosis
In vivo
Parenchyma
Tumor-Associated Macrophages
medicine
Animals
two-photon microscopy
Lung cancer
RC254-282
Original Research
Mice, Knockout
Microglia
cerebral metastasis
business.industry
Brain Neoplasms
Lewis lung carcinoma
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
macrophages
Mice, Inbred C57BL
Disease Models, Animal
lung cancer
medicine.anatomical_structure
Microscopy, Fluorescence, Multiphoton
Cancer research
Female
business
Brain metastasis
Subjects
Details
- ISSN :
- 14765586
- Volume :
- 23
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Neoplasia (New York, N.Y.)
- Accession number :
- edsair.doi.dedup.....92bc7587c4fd40eefee96e63f680896d