CD34+ cells contribute to the growing tumor vasculature in Ewing's sarcoma tumors.

LEE, TIM H.; BOLONTRADE, MARCELA F.; WORTH, LAURA L.; KLEINERMAN, EUGENIE S.

Philadelphia, Pennsylvania.

Simposio; 44to Encuentro y Exposición Anual. American Society of Hematology (ASH).; 2002

American Society of Hematology (ASH).

The 2 year metastasis-free survival for Ewing´s sarcoma, a neuroectodermal tumor that occurs in both bone and soft tissue, has been stagnant for the past 15 years. Understanding the biology of tumor growth may identify new therapeutic approaches. The purpose of these studies was to determine whether CD34+ stem cells contribute to the neovascularization process that supports the growth of Ewing´s sarcoma. CD34+ cells contain cells with endothelial precursor potential, which can engraft and proliferate in the bone marrow of sub-lethally irradiated SCID mice. Using our recently developed TC71 Ewing´s sarcoma SCID mouse model and umbilical cord blood as a source of CD34+ cells, we demonstrated that CD34+ cells specifically home to the neovascular area of Ewing´s sarcoma tumor in vivo. Human umbilical cord CD34+ cells isolated by immunomagnetic cell separation were transplanted into sub-lethally irradiated SCID mice. Engraftment of cord blood CD34+cells in SCID mice has been shown to occur as early as 7 days post-transplantation. Mice receiving no cord blood CD34+ cells died within two weeks following irradiation. Cord blood CD34+ cell recipient mice were then injected subcutaneously human TC71 tumor cells at 7 days post-transplantation. Tumors were allowed to grow for 2 weeks then harvested and subjected to immunohistochemical analysis. Reconstitution of bone marrow by cord blood CD34+ cells was confirmed after sacrifice at 3 weeks by harvesting and attaining the bone marrow for the human HLA antigen. Fluorescent co-staining of tumor sections for hHLA and mouse endothelial cell markers indicated involvement of donor-derived cells in the tumor vessels. We therefore concluded that these CD34+ cells migrated from the bone marrow to the growing tumor areas. These data indicate that vasculogenesis in addition to angiogenesis may contribute to Ewing´s sarcoma growth and development and suggest that CD34+ cells may provide a mechanism to deliver specific genes to the tumor site.