Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model

Tsukamoto, Shinji; Honoki, Kanya; Fujii, Hiromasa; Tohma, Yasuaki; Kido, Akira; Mori, Toshio; Tsujiuchi, Toshifumi; Tanaka, Yasuhito

doi:10.3892/ijo.2011.1220

Cited by 48 publications

(36 citation statements)

References 48 publications

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“…Exogenous MSCs could target the OS site and promote OS growth and progression in a mouse xenograft model [122]. Similar results were also found in a rat model [123]. IL-6 secreted by MSCs could activate STAT3 signaling in OS cells, which in turn augment cell proliferation, migration, invasion, and pulmonary metastasis [124].…”

Section: Stromal Niche: Bone Marrow Mesenchymal Stem Cellsupporting

confidence: 58%

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Mai¹,

Zhang²,

Xie³

et al. 2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma (OS) is the most common malignant primary bone tumor in children and adolescents and features rapid development, strong metastatic ability, and poor prognosis. It has been well established that diverse genetic aberrations and metabolic alterations confer the tumorigenesis and development of OS. The intricate metabolism and vascularization that contributes to the nutrient and structural support for tumor progression should be thoroughly clariied to help us gain novel insights into OS and its clinical diagnoses and treatments. With regard to the complex bone extracellular matrix (ECM) and local cell populations, we intend to illustrate the interrelationship between various microenvironmental signals and the diferent stages of OS evolution. Solid evidence has noted two crucial factors of the OS microenvironment in the acquisition of stem cell phenotypes -transforming growth factor-β1 (TGF-β1) signaling and hypoxia. Diferent cell subtypes in the local environment might also serve as unique contributors that interact with each other and communicate with distant cells, thus participating in local invasion and metastasis. Proper models have been established and improved to reveal the evolutionary footsteps of how normal cells transform into a neoplastic state and progress toward malignancy.

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Section: Stromal Niche: Bone Marrow Mesenchymal Stem Cellsupporting

confidence: 58%

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Mai¹,

Zhang²,

Xie³

et al. 2017

Osteosarcoma - Biology, Behavior and Mechanisms

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“…In addition, a study showed that B16 melanoma cells transplanted into allogeneic mice did not form tumors unless co-injected with MSCs (8). Subcutaneous inoculation of COS1NR cells followed by intravenous injection of MSCs at weeks 3 and 5 significantly increased the number of lung nodules (9). It has also been demonstrated that MSCs enhance the survival of follicular lymphoma B cells derived from human tumors.…”

Section: Introductionmentioning

confidence: 99%

Homologous mesenchymal stem cells promote the emergence and growth of pulmonary metastases of the rat osteosarcoma cell line UMR-106

et al. 2014

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Osteosarcoma (OS) is the most frequent primary bone sarcoma and tends to develop pulmonary metastasis. Studies have shown that mesenchymal stem cells (MSCs) are involved in OS growth and metastasis, but the mechanism remains unclear. The aim of the present study was to identify whether homologous MSCs could promote the growth and metastasis of OS in rats with a normal immune system. The OS cell line, UMR-106, which originally derives from a Sprague-Dawley (SD) rat-transplantable osteogenic sarcoma with an osteoblastic phenotype, has a strong carcinogenic capability and a high lung metastasis. Xenotransplanted models of UMR-106 with or without MSCs injected through the tibia (IT) or caudal vein (IV) were established. SD rats were randomly divided into six groups: Control, UMR-106 (IT), MSCs (IV), UMR-106 (IT) + MSCs (IV), UMR-106 (IV) and UMR-106 (IV) + MSCs (IV). Following injection, all rats were sacrificed at week 5, and the volume and quantity of metastatic sarcoma and the serum alkaline phosphatase levels were measured. There was no metastatic sarcoma in the liver, spleen and kidney in all groups. The rats in the MSCs (IV) + UMR-106 (IV) group showed a significantly higher volume and number of pulmonary metastatic tumors than those of the UMR-106 (IV) group. In pulmonary metastatic tissues, MSCs were found in the MSCs (IV) + UMR-106 (IV) group, but not in the UMR-106 (IT) + MSCs (IV) group. Notably, the expression of vascular endothelial growth factor (VEGF) was increased in the MSCs + UMR-106 cells co-culture system. The present study indicated that MSCs can significantly promote the pulmonary metastasis of the rat OS cell line, UMR-106, with a normal immune system, and VEGF was involved in MSC-promoted UMR-106 emergence and growth of pulmonary metastasis.

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“…Moreover, it is extremely useful for cancer stem cell research of bone tumors, where orthotopic injections of small number of cancer cells are required to demonstrate tumor initiating potential of cellular populations having stem-like properties, since establishment of tumors is dependent on the number of tumor initiating cells within cells transplanted [24]. Furthermore, several reports demonstrate that co-injection of human cancer cells with human stromal cells enhances tumor growth, suggesting the significance of proper tumor microenvironment [8, 25]. It would be interesting to compare tumor growth between injection of human osteosarcoma cells alone and co-injection of osteosarcoma cells with human stromal cells, using our established model as a future study.…”

Section: Discussionmentioning

confidence: 99%

An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma

Sasaki

Iyer

Sasaki

et al. 2015

Analytical Biochemistry

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Osteosarcoma, the most common type of primary bone cancer, is the second highest cause of cancer-related death in pediatric patients. To understand the mechanisms behind osteosarcoma progression and to discover novel therapeutic strategies for this disease, a reliable and appropriate mouse model is essential. For this purpose, osteosarcoma cells need to be injected into the bone marrow. Previously, the intratibial and intrafemoral injection methods were reported; however, the major drawback of these methods is the potential leakage of tumor cells from the injection site during or after these procedures. To overcome this, we have established an improved method to minimize leakage in an orthotopic mouse model of osteosarcoma. By taking advantage of the anatomical benefits of the femur with less bowing and larger medullary cavity than those of the tibia, osteosarcoma cells are injected directly into the femoral cavity following reaming of its intramedullary space. To prevent potential leakage of tumor cells during and after the surgery, the injection site is sealed with bone wax. This method requires a minor surgery of approximately 15 minutes under anesthesia. Our established orthotopic osteosarcoma model could serve as a valuable and reliable tool for examining tumor progression of various types of bone tumors.

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Mesenchymal stem cells promote tumor engraftment and metastatic colonization in rat osteosarcoma model

Cited by 48 publications

References 48 publications

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Homologous mesenchymal stem cells promote the emergence and growth of pulmonary metastases of the rat osteosarcoma cell line UMR-106

An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma

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