An Experimental Liver Metastasis Mouse Model Suitable for Short and Long‐Term Intravital Imaging

Marvin, Dieuwke L.; Dijke, Peter ten; Ritsma, Laila

doi:10.1002/cpz1.116

Cited by 4 publications

(4 citation statements)

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“…The best combination of strategies for optical access and image acquisition will depend on the cancer type and biological question asked. Dedicated protocols for the imaging of primary cancers, metastases and the tumor microenvironment in different sites help identify the optimal strategy (92)(93)(94)(95).…”

Section: Recent Protocols and Window Optimizations For Ivmmentioning

confidence: 99%

Volume imaging to interrogate cancer cell-tumor microenvironment interactions in space and time

Almagro

Messal

2023

Front. Immunol.

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Volume imaging visualizes the three-dimensional (3D) complexity of tumors to unravel the dynamic crosstalk between cancer cells and the heterogeneous landscape of the tumor microenvironment (TME). Tissue clearing and intravital microscopy (IVM) constitute rapidly progressing technologies to study the architectural context of such interactions. Tissue clearing enables high-resolution imaging of large samples, allowing for the characterization of entire tumors and even organs and organisms with tumors. With IVM, the dynamic engagement between cancer cells and the TME can be visualized in 3D over time, allowing for acquisition of 4D data. Together, tissue clearing and IVM have been critical in the examination of cancer-TME interactions and have drastically advanced our knowledge in fundamental cancer research and clinical oncology. This review provides an overview of the current technical repertoire of fluorescence volume imaging technologies to study cancer and the TME, and discusses how their recent applications have been utilized to advance our fundamental understanding of tumor architecture, stromal and immune infiltration, vascularization and innervation, and to explore avenues for immunotherapy and optimized chemotherapy delivery.

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Section: Recent Protocols and Window Optimizations For Ivmmentioning

confidence: 99%

Volume imaging to interrogate cancer cell-tumor microenvironment interactions in space and time

Almagro

Messal

2023

Front. Immunol.

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“…Next, we investigated the role of TGF-β in B16F10 cells in liver metastasis in vivo. To induce experimental liver metastases, we injected clonal B16F10 cell lines containing either the dox inducible caALK5 or kiALK5 in the mesenteric vein of C57BL/6J mice [18]. Clonal cell lines were selected based on similar caALK5 and kiALK5 expression (Figure S3A,B).…”

Section: Metastatic Liver Outgrowth Of B16f10 Cells Is Enhanced Upon ...mentioning

confidence: 99%

“…Clonal cell lines were selected based on similar caALK5 and kiALK5 expression (Figure S3A,B). To induce ALK5 expression, the mice were treated with control chow or chow containing dox (625 mg/kg) and dox treatment of cells was started one day prior to injection (Figure 3A) [18]. The induced expression of ALK5 could be detected at the protein level, although levels varied, possibly due to differential contributions of metastasis in protein samples (Figure S3C).…”

Section: Metastatic Liver Outgrowth Of B16f10 Cells Is Enhanced Upon ...mentioning

confidence: 99%

“…Mice were put on control or doxycycline-containing chow (625 mg/kg, #A153D70620, Bio-Services, Uden, The Netherlands) one day prior to surgery. Mice were injected with 5 × 10 5 B16F10 cells containing caALK5 or kiALK5 expression constructs using a mesenteric vein injection [18]. Doxycycline-containing food was replaced every two to three days.…”

Section: Animal Studiesmentioning

confidence: 99%

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TGF-β Type I Receptor Signaling in Melanoma Liver Metastases Increases Metastatic Outgrowth

Marvin,

Dijkstra,

Zulfiqar

et al. 2023

IJMS

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Despite advances in treatment for metastatic melanoma patients, patients with liver metastasis have an unfavorable prognosis. A better understanding of the development of liver metastasis is needed. The multifunctional cytokine Transforming Growth Factor β (TGF-β) plays various roles in melanoma tumors and metastasis, affecting both tumor cells and cells from the surrounding tumor microenvironment. To study the role of TGF-β in melanoma liver metastasis, we created a model to activate or repress the TGF-β receptor pathway in vitro and in vivo in an inducible manner. For this, we engineered B16F10 melanoma cells to have inducible ectopic expression of a constitutively active (ca) or kinase-inactive (ki) TGF-β receptor I, also termed activin receptor-like kinase (ALK5). In vitro, stimulation with TGF-β signaling and ectopic caALK5 expression reduced B16F10 cell proliferation and migration. Contrasting results were found in vivo; sustained caALK5 expression in B16F10 cells in vivo increased the metastatic outgrowth in liver. Blocking microenvironmental TGF-β did not affect metastatic liver outgrowth of both control and caALK5 expressing B16F10 cells. Upon characterizing the tumor microenvironment of control and caALk5 expressing B16F10 tumors, we observed reduced (cytotoxic) T cell presence and infiltration, as well as an increase in bone marrow-derived macrophages in caALK5 expressing B16F10 tumors. This suggests that caALK5 expression in B16F10 cells induces changes in the tumor microenvironment. A comparison of newly synthesized secreted proteins upon caALK5 expression by B16F10 cells revealed increased secretion of matrix remodeling proteins. Our results show that TGF-β receptor activation in B16F10 melanoma cells can increase metastatic outgrowth in liver in vivo, possibly through remodeling of the tumor microenvironment leading to altered infiltration of immune cells. These results provide insights in the role of TGF-β signaling in B16F10 liver metastasis and could have implications regarding the use of TGF-β inhibitors for the treatment of melanoma patients with liver metastasis.

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Intravital microscopy

Fonseca

Schnoor

Vadillo

2022

Cell Movement in Health and Disease

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An Experimental Liver Metastasis Mouse Model Suitable for Short and Long‐Term Intravital Imaging

Cited by 4 publications

References 64 publications

Volume imaging to interrogate cancer cell-tumor microenvironment interactions in space and time

Volume imaging to interrogate cancer cell-tumor microenvironment interactions in space and time

TGF-β Type I Receptor Signaling in Melanoma Liver Metastases Increases Metastatic Outgrowth

Intravital microscopy

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