Model for human tumor sngiogenesis using NOD/SCID mice

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Angiogenesis is a crucial event for cancer. We examined human tumor angiogenesis using transplantation of human bone and human breast carcinoma (MB-231) or neuroblastoma (SK-N-DZ) cells into subcutaneous tissue of NOD/SCID mice. Human vessels were observed by immunohistochemical stainings with anti-human CD31 and CD34 antibodies. As a result, human tumor angiogenesis was observed in all transplanted human cancer tissues. Expression vectors (Tek-Fc or Flt-Fc) containing Tek/Tie-2 or Flt-1-extracellular domain and human immunoglobulin Fc domain were transferred into MB-231 or SK-N-DZ cells. Clones with Tek-Fc, Flt-Fc, or neor were inoculated into human bone transplanted-NOD/SCID mice. As a result, tumors which formed by not only the Flt-Fc clones but also the Tek-Fc clones were smaller than tumors formed by neor clones. The tumor vessel density in the tumors of Flt-Fc clones was significantly decreased compared with the tumors of neor clones. In the other hand, the deformity of tumor vessels and the decreased density of vessel were observed in the tumors of Tek-Fc clones. It is obscure whether tumor angiogenesis in hematological malignancies is essential for the tumor development. We examined whether human tumor angiogenesis was generated in these tumors by the inoculation of human leukemia/lymphoma or myeloma cells into the transplanted human bone. As a result, the microvessels in tumors of the leukemia or myeloma cells were formed by human endothelia, which expressed human CD31 and CD34. The microvessel density of the tumors was significantly higher than one of the transplanted human bones without leukemic or myeloma cells (p<0.01). The in vivo models for human tumor angiogenesis were established using the transplantation of human bone and human cancer cells into NOD/SCID mice. These models may be useful for the development of new cancer therapies.