Development and Biological Analysis of a Novel Orthotopic Peritoneal Dissemination Mouse Model Generated Using a Pancreatic Ductal Adenocarcinoma Cell Line

Yanagihara, Kazuyoshi; Kubo, Takanori; Mihara, Keichiro; Kuwata, Takeshi; Ochiai, Atsushi; Seyama, Toshio; Yokozaki, Hiroshi

doi:10.1097/mpa.0000000000001253

Cited by 6 publications

(13 citation statements)

References 45 publications

(56 reference statements)

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“…These mice are unable to generate an immune response against human cells and tumor engraftment is thus promoted in the peritoneal cavity. The xenografted PCa models have been studied using colon cancer (HCT-116, LS174T, HT29, SW480, SW620, LoVo, RKO, Caco-2, KM12, MDST8, HUTU80) [ 57 , 58 , 59 , 60 , 61 ], pancreatic cancer (Panc-1, TCC-Pan2, BxPC3, AsPC-1) [ 62 , 63 , 64 ], gastric cancer (60As6, HSC-44PE, HSC-58, MKN45-P) [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ], and ovarian cancer (OVCAR3, OVCAR4, OVCAR5, OVCAR8, CAOV3, OVSAHO, OV2944-HM-1, SKOV-3) [ 59 , 70 , 71 , 72 ] cell lines. These models have been used to attain proofs of concept and explore treatments that determine in vivo tumor cell cytotoxicity of drugs, such as chemotherapeutic agents.…”

Section: Pca Mouse Modelsmentioning

confidence: 99%

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

Bella

Trani

Fernandez‐Sendin

et al. 2021

Cancers

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Peritoneal carcinomatosis of primary tumors originating in gastrointestinal (e.g., colorectal cancer, gastric cancer) or gynecologic (e.g., ovarian cancer) malignancies is a widespread type of tumor dissemination in the peritoneal cavity for which few therapeutic options are available. Therefore, reliable preclinical models are crucial for research and development of efficacious treatments for this condition. To date, a number of animal models have attempted to reproduce as accurately as possible the complexity of the tumor microenvironment of human peritoneal carcinomatosis. These include: Syngeneic tumor cell lines, human xenografts, patient-derived xenografts, genetically induced tumors, and 3D scaffold biomimetics. Each experimental model has its own strengths and limitations, all of which can influence the subsequent translational results concerning anticancer and immunomodulatory drugs under exploration. This review highlights the current status of peritoneal carcinomatosis mouse models for preclinical development of anticancer drugs or immunotherapeutic agents.

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Section: Pca Mouse Modelsmentioning

confidence: 99%

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

Bella

Trani

Fernandez‐Sendin

et al. 2021

Cancers

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“…Four-week-old female SCID mice were purchased from CLEA Japan (Tokyo, Japan) and maintained under specific pathogen-free conditions, as detailed previously [22]. The PDCLs were engrafted into the mice SC or by OI.…”

Section: Methodsmentioning

confidence: 99%

“…Few high-passage pancreatic cancer cell lines are currently available commercially [6]. We previously established PDA cell lines derived from the ascites or PDX tumors of patients (Taco series) [22, 25].…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of Patient-Derived Tumor Models of Pancreatic Ductal Adenocarcinoma Involving Orthotopic Implantation

et al. 2022

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Background: Pancreatic ductal adenocarcinoma (PDA) is associated with very poor prognoses. Therefore, new therapies and preclinical models are urgently needed. In the present study, we sought to develop more realistic experimental models for use in PDA research. Methods: We developed patient-derived xenografts (PDXs), established PDX-derived cell lines (PDCLs), and generated cell line-derived xenografts (CDXs), which we integrated to create 13 matched “trios” – i.e., patient-derived tumor models of PDA. We then compared and contrasted histological and molecular alterations between these three model systems. Results: Orthotopic implantation (OI) of the PDCLs resulted in tumorigenesis and metastases to the liver and peritoneum. Morphological comparisons of OI-CDXs and OI-PDXs with passaged tumors revealed that the histopathological features of the original tumor were maintained in both models. Molecular alterations in PDX tumors (including those to KRAS, TP53, SMAD4, and CDKN2A) were similar to those in the respective PDCLs and CDX tumors. When gene expression levels in the PDCLs, ectopic tumors, and OI tumors were compared, the distant metastasis-promoting gene CXCR4 was specifically upregulated in OI tumors, whose immunohistochemical profiles suggested epithelial-mesenchymal transition and adeno-squamous trans-differentiation. Conclusion: These patient-derived tumor models provide useful tools for monitoring responses to antineoplastic agents and for studying PDA biology.

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“…However, luciferase can be genetically engineered into the PDAC cell lines to be implanted, allowing for much easier tumor imaging by measuring intensity of bioluminescence [ 102 ]. Other methods of syngeneic cell line delivery include intravenous, intraperitoneal, and intrasplenic, which have been used to provide models for lung, peritoneal, lymph node, and liver metastasis, respectively [ 110 , 111 , 112 ]. Our group is currently developing the syngeneic KPC cell line model system for studying VSV-based OV therapy against PDAC (i.e., location, tumor microenvironment, immune system), without the high costs and long development times of GEMM models.…”

Section: Overview Of Common Experimental Models To Study Ov Therapmentioning

confidence: 99%

Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

Holbrook

Goad

Grdzelishvili

2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. However, some PDAC cell lines are resistant to VSV. Upregulated type I IFN signaling and constitutive expression of a subset of interferon-simulated genes (ISGs) play a major role in such resistance, while other mechanisms, such as inefficient viral attachment and resistance to VSV-mediated apoptosis, also play a role in some PDACs. Several alternative approaches have been shown to break the resistance of PDACs to VSV without compromising VSV oncoselectivity, including (i) combinations of VSV with JAK1/2 inhibitors (such as ruxolitinib); (ii) triple combinations of VSV with ruxolitinib and polycations improving both VSV replication and attachment; (iii) combinations of VSV with chemotherapeutic drugs (such as paclitaxel) arresting cells in the G2/M phase; (iv) arming VSV with p53 transgenes; (v) directed evolution approach producing more effective OVs. The latter study demonstrated impressive long-term genomic stability of complex VSV recombinants encoding large transgenes, supporting further clinical development of VSV as safe therapeutics for PDAC.

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Development and Biological Analysis of a Novel Orthotopic Peritoneal Dissemination Mouse Model Generated Using a Pancreatic Ductal Adenocarcinoma Cell Line

Abstract: Supplemental digital content is available in the text.

Cited by 6 publications

References 45 publications

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications

A Comparative Study of Patient-Derived Tumor Models of Pancreatic Ductal Adenocarcinoma Involving Orthotopic Implantation

Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions

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