Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

Yu, Kyeong-Nam; Minai-Tehrani, Arash; Chang, Simyung; Hwang, Sung‐Joo; Hong, Sun; Kim, Jieun; Shin, Ji‐Young; Park, Sung Jin; Kim, Jihye; Kwon, Jung-Taek; Jiang, Hu‐Lin; Kang, Bitna; Kim, Duyeol; Chae, Chanhee; Lee, Kee-Ho; Yoon, Tae‐Jong; Beck, George R.; Cho, Myung‐Haing

doi:10.1371/journal.pone.0015623

Cited by 24 publications

(10 citation statements)

References 42 publications

(44 reference statements)

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“…11 , 50 - 52 OPN inhibition decreases local breast cancer growth and metastasis. 17 , 28 , 29 , 53 - 55 Therefore, OPN has been proposed as an anti-cancer target. Studies suggest that OPN-integrin binding via the RGD domain stimulates tumor cell invasiveness and migration, in part through activation of MMPs/uPA.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin mediates an MZF1–TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer

et al. 2014

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Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TMEN) significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN−) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype. This OPN-TGF-β1 pathway requires the transcription factor, myeloid zinc finger 1 (MZF1). In vivo studies with xenotransplant models in NOD-scid mice showed that OPN expression increases cancer growth and metastasis by mediating MSC-to-CAF transformation in a process that is MZF1- and TGF-β1-dependent. We conclude that tumor-derived OPN engenders MSC-to-CAF transformation in the microenvironment to promote tumor growth and metastasis via the OPN-MZF1-TGF-β1 pathway.

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Section: Discussionmentioning

confidence: 99%

Osteopontin mediates an MZF1–TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer

et al. 2014

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“…al. used an orthotopic mouse breast cancer model that metastasized to the lungs (98). Two weeks after tumor inoculation, shRNA against OPN was delivered as an aerosol into the lungs of the mice.…”

Section: Introductionmentioning

confidence: 99%

Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

Sawyer

Kyriakides

2016

Advanced Drug Delivery Reviews

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Extracellular matrix is composed by a complex array of molecules that together provide structural and functional support to cells. These properties are mainly mediated by the activity of collagenous and elastic fibers, proteoglycans, and proteins such as fibronectin and laminin. ECM composition is tissue-specific and could include matricellular proteins whose primary role is to modulate cell-matrix interactions. In adults, matricellular proteins are primarily expressed during injury, inflammation and disease. Particularly, they are closely associated with the progression and prognosis of cardiovascular and fibrotic diseases, and cancer. This review aims to provide an overview of the potential use of matricellular proteins in drug delivery including the generation of therapeutic agents based on the properties and structures of these proteins as well as their utility as biomarkers for specific diseases.

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“…It can be used in patients with cardiac, cerebral or peripheral vascular diseases, as well as kidney, liver or lung diseases. In fact, our research group has demonstrated that aerosol delivery of therapeutic genes/molecules has excellent and sustained effects on lung tumorigenesis [14,15,16,17,18]. Therefore, aerosol delivery of DHE could provide a novel approach with the potential for use in lung cancer, and this study is currently under way.…”

Section: Discussionmentioning

confidence: 99%

Dihydroergotamine Tartrate Induces Lung Cancer Cell Death through Apoptosis and Mitophagy

Chang¹,

Lee²,

Yu³

et al. 2016

Chemotherapy

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Background: Mitochondria have emerged as a major target for anticancer therapy because of their critical role in cancer cell survival. Our preliminary works have suggested that dihydroergotamine tartrate (DHE), an antimigraine agent, may have effects on mitochondria. Methods: We examined the effect of DHE on the survival of several lung cancer cells and confirmed that DHE suppressed diverse lung cancer cell growth effectively. To confirm whether such effects of DHE would be associated with mitochondria, A549 cells were employed for the evaluation of several important parameters, such as membrane potential, reactive oxygen species (ROS) generation, apoptosis, ATP production and autophagy. Results: DHE decreased membrane permeability, increased ROS generation as well as apoptosis, and disturbed ATP production. Eventually, mitophagy was activated for damaged mitochondria. Conclusion: Taken together, our findings demonstrate that DHE induces lung cancer cell death by the induction of apoptosis and mitophagy, thus suggesting that DHE can be developed as an anti-lung cancer therapeutic agent.

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Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

Cited by 24 publications

References 42 publications

Osteopontin mediates an MZF1–TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer

Osteopontin mediates an MZF1–TGF-β1-dependent transformation of mesenchymal stem cells into cancer-associated fibroblasts in breast cancer

Matricellular proteins in drug delivery: Therapeutic targets, active agents, and therapeutic localization

Dihydroergotamine Tartrate Induces Lung Cancer Cell Death through Apoptosis and Mitophagy

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