Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model

Seo, Kyoung Won; Lee, Hee Woo; Oh, Ye In; Ahn, Jin Ok; Koh, Ye Rin; Oh, Seung Hyun; Kang, Sung Keun; Youn, Hwa Young

doi:10.3109/14653249.2011.584864

Cited by 39 publications

(26 citation statements)

References 52 publications

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“…Although we did not test for the apoptotic effect of cAT-MSC-IFN- β in vitro , our in vivo data demonstrate that the treatment with cAT-MSC-IFN- β can induce an apoptotic response in tumor-bearing nude mice. These results are supported by several other studies in which IFN- β had an apoptotic and growth inhibitory effect on melanoma cells [16], [23], [30]. Induction of apoptosis by IFN- β involved FADD/caspase-8 signaling, activation of the caspase cascade, release of cytochrome c from mitochondria, disruption of mitochondrial potential, changes in plasma membrane integrity, and DNA fragmentation [22], [47].…”

Section: Discussionsupporting

confidence: 79%

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Anti-Tumor Effect of Adipose Tissue Derived-Mesenchymal Stem Cells Expressing Interferon-β and Treatment with Cisplatin in a Xenograft Mouse Model for Canine Melanoma

et al. 2013

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Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell-therapy vehicles for the delivery of anti-tumor molecules into the tumor microenvironment. The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, including cytokines, interferon, and pro-drugs. The present study was designed to determine the possibility that the combination of stem cell-based gene therapy with low-dose cisplatin would improve therapeutic efficacy against canine melanoma. The IFN-β transduced canine AT-MSCs (cAT-MSC-IFN-β) inhibited the growth of LMeC canine melanoma cells in direct and indirect in vitro co-culture systems. In animal experiments using BALB/c nude mouse xenografts, which developed by injecting LMeC cells, the combination treatment of cAT-MSC-IFN-β and low-dose cisplatin significantly reduced tumor volume compared with the other treatment groups. Fluorescent microscopic analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay of tumor section provided evidence for homing of cAT-MSC-IFN-β to the tumor site and revealed that the combination treatment of cAT-MSC-IFN-β with low-dose cisplatin induced high levels of cell apoptosis. These findings may prove useful in further explorations of the application of these combined approaches to the treatment of malignant melanoma and other tumors.

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Section: Discussionsupporting

confidence: 79%

“…The lentiviral vector carrying the canine interferon beta gene (cIFN- β ) was generated as described previously [30]. Briefly, the target gene amplified by PCR from canine thymus cDNA was cloned into the pLenti6/V5-D-TOPO® vector using the pLenti/V5 Directional TOPO Cloning Kit (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Anti-Tumor Effect of Adipose Tissue Derived-Mesenchymal Stem Cells Expressing Interferon-β and Treatment with Cisplatin in a Xenograft Mouse Model for Canine Melanoma

et al. 2013

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“…IFNs have previously been shown to potentiate the cytotoxic effect of all chemicals tested in this study: HU [32,33], 5-FU [34,35], MTX [36] and cisPt [37,38]. Yonekura et al [39] have even proposed that Hsp27 plays a crucial role in the IFN-γ-induced sensitization of oral squamous cell carcinoma cells to anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Matijević¹,

Kirinec²,

Pavelić³

2011

Chemotherapy

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Background: Toll-like receptor 3 (TLR3) activation in tumor cells induces apoptosis. We investigated the effect of TLR3 ligand (poly(I:C)) in combination with chemotherapeutics applied to human pharyngeal carcinoma cells as a possible antitumor therapy. Methods:Human pharyngeal cancer cell lines were studied (FaDu and Detroit 562). Cytotoxicity assays and apoptosis assays (annexin V staining and caspase 3/7 activity measurements) were used to investigate the cytotoxic effects. By using TLR3 siRNA we confirmed that the observed effect is TLR3-dependent. Results: We found that the combined application of poly(I:C) and chemotherapeutics (cisPt, HU, 5-FU and MTX) has a stronger inhibitory effect on cell growth in tumor cells expressing functional TLR3 as compared with a single treatment. This is a result of TLR3-dependent apoptosis. Conclusion: Our study showed that a combined application of the two agents already being used in tumor therapy could lower the necessary dosage of chemotherapeutics, leading to fewer side effects.

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“…Human bone marrow MSC secreting interferon (IFN) – β has been proven to have success in diminishing a number of tumors such as melanoma, 30 breast cancer 31 and lung metastases 32 . In a recently published study, amniotic fluid derived mesenchymal stem cells (AF‑MSCs) were isolated, investigated for their tumor tropism and capability to transport interferon‑β (IFNβ) to the region of neoplasia in a bladder tumor model.…”

Section: Stem Cell Sources and Their Homing To Tumorsmentioning

confidence: 99%

Encapsulated stem cells for cancer therapy

Shah

2013

Biomatter

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Stem cells have inherent tumor‑trophic migratory properties and can serve as vehicles for delivering effective, targeted therapy to isolated tumors and metastatic disease, making them promising anti‑cancer agents. Encapsulation of therapeutically engineered stem cells in hydrogels has been utilized to provide a physical barrier to protect the cells from hostile extrinsic factors and significantly improve the therapeutic efficacy of transplanted stem cells in different models of cancer. This review aims to discuss the potential of different stem cell types for cancer therapy, various engineered stem cell based therapies for cancer, stem cell encapsulation process and provide an in depth overview of current applications of therapeutic stem cell encapsulation in the highly malignant brain tumor, glioblastoma multiforme (GBM), as well as the prospects for their clinical translation.

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Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model

Cited by 39 publications

References 52 publications

Anti-Tumor Effect of Adipose Tissue Derived-Mesenchymal Stem Cells Expressing Interferon-β and Treatment with Cisplatin in a Xenograft Mouse Model for Canine Melanoma

Anti-Tumor Effect of Adipose Tissue Derived-Mesenchymal Stem Cells Expressing Interferon-β and Treatment with Cisplatin in a Xenograft Mouse Model for Canine Melanoma

Antitumor Activity from the Combined Application of Poly(I:C) and Chemotherapeutics in Human Metastatic Pharyngeal Cell Lines

Encapsulated stem cells for cancer therapy

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