An orthotopic xenograft model with survival hindlimb amputation allows investigation of the effect of tumor microenvironment on sarcoma metastasis

详细信息    查看全文

• 作者：Seth D. Goldstein ; Masanori Hayashi…
• 关键词：Ewing sarcoma ; Osteosarcoma ; Rhabdomyosarcoma ; Arginase ; Metastasis ; Animal model
• 刊名：Clinical & Experimental Metastasis
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：32
• 期：7
• 页码：703-715
• 全文大小：2,405 KB
• 参考文献：1.Adamson PC, Blaney SM (2005) New approaches to drug development in pediatric oncology. Cancer J 11:324-30CrossRef PubMed
  2.Khanna C, Fan TM, Gorlick R et al (2014) Toward a drug development path that targets metastatic progression in osteosarcoma. Clin Cancer Res 20:4200-209PubMed Central CrossRef PubMed
  3.Kern SE, Shibata D (2007) The fuzzy math of solid tumor stem cells: a perspective. Cancer Res 67:8985-988CrossRef PubMed
  4.Krishnan K, Khanna C, Helman LJ (2005) The biology of metastases in pediatric sarcomas. Cancer J 11:306-13CrossRef PubMed
  5.Wan L, Pantel K, Kang Y (2013) Tumor metastasis: moving new biological insights into the clinic. Nat Med 19:1450-464CrossRef PubMed
  6.Morton CL, Houghton PJ (2007) Establishment of human tumor xenografts in immunodeficient mice. Nat Protoc 2:247-50CrossRef PubMed
  7.Johnson JI, Decker S, Zaharevitz D et al (2001) Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 84:1424-431PubMed Central CrossRef PubMed
  8.Kerbel RS (2003) Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans: better than commonly perceived-but they can be improved. Cancer Biol Ther 2:S134–s139PubMed
  9.Norris RE (2012) Adamson PC Challenges and opportunities in childhood cancer drug development. Nat Rev Cancer 12:776-82CrossRef PubMed
  10.Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: The arrive guidelines for reporting animal research. PLoS Biol 8:e1000412PubMed Central CrossRef PubMed
  11.Hussain SP, Trivers GE, Hofseth LJ et al (2004) Nitric oxide, a mediator of inflammation, suppresses tumorigenesis. Cancer Res 64:6849-853CrossRef PubMed
  12.Smith MA, Maris JM, Lock R et al (2011) Initial testing (stage 1) of the polyamine analog PG11047 by the pediatric preclinical testing program. Pediatr Blood Cancer 57:268-74PubMed Central CrossRef PubMed
  13.Yan X, Takahara M, Xie L et al (2011) Arginine metabolism in soft tissue sarcoma. J Dermatol Sci 61:211-15CrossRef PubMed
  14.Williams EL (2005) Djamgoz MBA Nitric oxide and metastatic cell behaviour. Bioessays 27:1228-238CrossRef PubMed
  15.Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423-437PubMed Central CrossRef PubMed
  16.Tanaka S, Saito Y, Kunisawa J et al (2012) Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rγKO mice. J Immunol 188:6145-155PubMed Central CrossRef PubMed
  17.Ito M, Hiramatsu H, Kobayashi K et al (2002) NOD/SCID/γc null mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100:3175-182CrossRef PubMed
  18.Berlin ?, Samid D, Donthineni-Rao R, Akeson W, Amiel D, Woods VL Jr (1993) Development of a novel spontaneous metastasis model of human osteosarcoma transplanted orthotopically into bone of athymic mice. Cancer Res 53:4890-895PubMed
  19.Huang P, Allam A, Taghian A, Freeman J, Duffy M, Suit HD (1995) Growth and metastatic behavior of five human glioblastomas compared with nine other histological types of human tumor xenografts in SCID mice. J Neurosurg 83:308-15CrossRef PubMed
  20.Khanna C, Prehn J, Yeung C, Caylor J, Tsokos M, Helman L (2000) An orthotopic model of murine osteosarcoma with clonally related variants differing in pulmonary metastatic potential. Clin Exp Metastasis 18:261-71CrossRef PubMed
  21.Luu HH, Kang Q, Jong KP et al (2005) An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis. Clin Exp Metastasis 22:319-29CrossRef PubMed
  22.Yuan J, Ossendorf C, Szatkowski JP et al (2009) Osteoblastic and osteolytic human osteosarcomas can be studied with a new xenograft mouse model producing spontaneous metastases. Cancer Investig 27:435-42CrossRef
  23.Duyverman AMMJ, Steller EJA, Fukumura D, Jain RK, Duda DG (2012) Studying primary tumor-associated fibroblast involvement in cancer metastasis in mice. Nat Protoc 7:756-62PubMed Central CrossRef PubMed
  24.Chao T, Greager JA (1997) Experimental pulmonary sarcoma metastases in athymic nude mice. J Surg Oncol 65:123-26CrossRef PubMed
  25.Pocard M, Tsukui H, Salmon R, Dutrillaux B, Poupon MF (1996) Efficiency of orthotopic xenograft models for human colon cancers. In Vivo 10:463-69PubMed
  26.Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170:793-04PubMed Central CrossRef PubMed
  27.Joo K, Kim J, Jin J et al (2013) Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ. Cell Rep 3:260-73CrossRef PubMed
  28.Kozlowski JM, Fidler IJ, Campbell D, Xu ZL, Kaighn ME, Hart IR (1984) Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Re
• 作者单位：Seth D. Goldstein (1)
  Masanori Hayashi (1)
  Catherine M. Albert (1)
  Kyle W. Jackson (1)
  David M. Loeb (1)
  
  1. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Bunting-Blaustein Cancer Research Building, Room 2M51, 1650 Orleans St., Baltimore, MD, 21231, USA
  
• 刊物主题：Cancer Research; Biomedicine general; Oncology; Hematology; Surgical Oncology;
• 出版者：Springer Netherlands
• ISSN：1573-7276

文摘

Overall survival rates for pediatric high-grade sarcoma have improved greatly in the past few decades, but prevention and treatment of distant metastasis remain the most compelling problems facing these patients. Traditional preclinical mouse models have not proven adequate to study the biology and treatment of spontaneous distant sarcoma metastasis. To address this deficit, we developed an orthotopic implantation/amputation model in which patient-derived sarcoma xenografts are surgically implanted into mouse hindlimbs, allowed to grow, then subsequently amputated and the animals observed for development of metastases. NOD/SCID/IL-2Rγ-null mice were implanted with either histologically intact high grade sarcoma patient-derived xenografts or cell lines in the pretibial space and affected limbs were amputated after tumor growth. In contrast to subcutaneous flank tumors, we were able to consistently detect spontaneous distant spread of the tumors using our model. Metastases were seen in 27-0 % of animals, depending on the xenograft, and were repeatable and predictable. We also demonstrate the utility of this model for studying the biology of metastasis and present preliminary new insights suggesting the role of arginine metabolism and macrophage phenotype polarization in creating a tumor microenvironment that facilitates metastasis. Subcutaneous tumors express more arginase than inducible nitric oxide synthase and demonstrate significant macrophage infiltration, whereas orthotopic tumors express similar amounts of inducible nitric oxide synthase and arginase and have only a scant macrophage infiltrate. Thus, we present a model of spontaneous distant sarcoma metastasis that mimics the clinical situation and is amenable to studying the biology of the entire metastatic cascade. Keywords Ewing sarcoma Osteosarcoma Rhabdomyosarcoma Arginase Metastasis Animal model