Intravital imaging of vascular anomalies and extracellular matrix remodeling in orthotopic pancreatic tumors

Bochner, Filip; Mohan, Vishnu; Zinger, Assaf; Golani, Ofra; Schroeder, Avi; Sagi, Irit; Neeman, Michal

doi:10.1002/ijc.32759

Cited by 12 publications

(8 citation statements)

References 36 publications

(70 reference statements)

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“…While recent advances have enabled intravital imaging of the pancreas, existing designs are still limited in either stability for long-term time-lapse imaging on the minutes time scale, or their ability to accommodate pancreata of a variety of sizes (e.g. healthy versus tumour bearing) [8,14,42].…”

Section: Discussionmentioning

confidence: 99%

SWIP—a stabilized window for intravital imaging of the murine pancreas

Adkisson

et al. 2022

Open Biol.

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Pancreatitis and pancreatic ductal adenocarcinoma (PDAC) are grave illnesses with high levels of morbidity and mortality. Intravital imaging (IVI) is a powerful technique for visualizing physiological processes in both health and disease. However, the application of IVI to the murine pancreas presents significant challenges, as it is a deep, compliant, visceral organ that is difficult to access, easily damaged and susceptible to motion artefacts. Existing imaging windows for stabilizing the pancreas during IVI have unfortunately shown poor stability for time-lapsed imaging on the minutes to hours scale, or are unable to accommodate both the healthy and tumour-bearing pancreata. To address these issues, we developed an improved stabilized window for intravital imaging of the pancreas (SWIP), which can be applied to not only the healthy pancreas but also to solid tumours like PDAC. Here, we validate the SWIP and use it to visualize a variety of processes for the first time, including (1) single-cell dynamics within the healthy pancreas, (2) transformation from healthy pancreas to acute pancreatitis induced by cerulein, and (3) the physiology of PDAC in both autochthonous and orthotopically injected models. SWIP can not only improve the imaging stability but also expand the application of IVI in both benign and malignant pancreas diseases.

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Section: Discussionmentioning

confidence: 99%

SWIP—a stabilized window for intravital imaging of the murine pancreas

Adkisson

et al. 2022

Open Biol.

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“…In the study of the TME, vascular remodeling has received particular attention as it impacts tumor nutrition, oxygenation, dissemination, and the recruitment of immune components. Quantitative assessments of the extent of tumor vascularization can be readily achieved by both tissue clearing and IVM, and have shown that several tumor types share a tendency to increase the vascular density within their mass ( 33 , 49 , 121 ). In some cancers the angiogenic capabilities may extend to lymphangiogenesis, as seen in pancreatic cancer ( 62 ).…”

Section: Applications Of Volume Imaging To Visualize Cell-tme Interac...mentioning

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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“…Several pharmacological and physical strategies aiming at modulating the TME to alleviate tumor fibrosis have been shown to improve the delivery and efficacy of drugs and drug nanoformulations. [13][14][15] Many TME remodeling strategies have specifically focused on nanomedicine formulations, such as liposomes and micelles. [16][17][18][19] Nanomedicines can accumulate in tumors relatively effectively and selectively, thereby improving therapeutic performance and minimizing side effects.…”

Section: Introductionmentioning

confidence: 99%

Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor‐Targeted Drug Delivery

Biancacci,

De Santis,

Rama

et al. 2023

Advanced Therapeutics

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The dense stromal matrix in fibrotic tumors hinders tumor‐targeted drug delivery. Tamoxifen (TMX), an estrogen receptor modulator that is clinically used for the treatment of breast cancer, is shown to reprogram the tumor microenvironment (TME) and to alleviate desmoplasia. It is investigated if TMX, administered in free and nano‐formulated form, can be repurposed as a TME remodeling agent to improve tumor accumulation of nano‐formulations in pancreatic ductal adenocarcinoma and triple‐negative breast cancer mouse models, evaluated using clinical‐stage Cy7‐labeled core‐crosslinked polymeric micelles (CCPM). Under control conditions, higher levels of Cy7‐CCPM are found in PANC‐1 tumors (16.7% ID g−1 at 48 h post i.v. injection) than in 4T1 tumors (11.0% ID g−1). In both models, free and nano‐formulated TMX failed to improve CCPM delivery. These findings are congruent with the results from histopathological immunofluorescence analysis of tumor tissue, which indicate that TMX treatment does not significantly change vascularization, perfusion, macrophage infiltration, collagen density, and collagen fiber thickness. Altogether, these results demonstrate that in PANC‐1 and 4T1 mouse models, TMX treatment does not contribute to beneficial TME priming and enhanced tumor‐targeted drug delivery.

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Intravital imaging of vascular anomalies and extracellular matrix remodeling in orthotopic pancreatic tumors

Cited by 12 publications

References 36 publications

SWIP—a stabilized window for intravital imaging of the murine pancreas

SWIP—a stabilized window for intravital imaging of the murine pancreas

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

Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor‐Targeted Drug Delivery

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