Interruption of tumor dormancy by a transient angiogenic burst within the tumor microenvironment
Interruption of tumor dormancy by a transient angiogenic burst within the tumor microenvironment
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DOI：
10.1073/pnas.0506200103
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发表时间：
2006-03-14
影响因子：
11.1
通讯作者：
Amadori, A
中科院分区：
文献类型：
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作者：
Indraccolo, S;Stievano, L;Amadori, A
肿瘤生长目前被认为是一种与新血管形成和血管生成因子持续产生相关的现象，但暂时的血管生成开关是否可能引发肿瘤生长仍不清楚。在这里，我们报告说，白血病细胞（MOLT-3）血管生成不良，并保持休眠时，注射s.c.免疫缺陷小鼠。然而，淋巴肿瘤的进行性生长总是记录时，从卡波西肉瘤（KS-IMM）的照射血管生成细胞局部共注射MOLT-3细胞或稍后给药。通过流式细胞术和实时PCR分析跟踪KS-IMM细胞在体内的持久性，并且其限于几天，在此期间诱导血管生成并先于肿瘤生长。其他类型的低致瘤性癌细胞的植入也大大提高了辐射KS-IMM细胞。此外，短期治疗血管生成因子，包括碱性FGF或VEGF，无论是作为重组因子或逆转录病毒载体提供，也加速肿瘤生长。这些发现可能强调，肿瘤血管生成是一个过程，需要更多的血管生成因子的诱导比维持。
Tumor growth is currently viewed as a phenomenon associated with neovascularization and sustained production of angiogenic factors, but whether a transient angiogenic switch may trigger tumor growth remains unclear. Here, we report that leukemia cells (MOLT-3) were poorly angiogenic and remained dormant when injected s.c. into immunodeficient mice. However, progressive growth of lymphoid tumors was invariably recorded when irradiated angiogenic cells from Kaposi's sarcoma (KS-IMM) were locally coinjected with MOLT-3 cells or administered later. The persistence of KS-IMM cells in vivo was tracked by flow cytometry and real-time PCR analysis, and it was limited to a few days, during which angiogenesis was induced and preceded tumor growth. The engraftment of other types of poorly tumorigenic cancer cells was also greatly improved by irradiated KS-IMM cells. Moreover, short-term treatment with angiogenic factors, including basic FGF or VEGF, either given as recombinant factors or delivered by retroviral vectors, also accelerated tumor growth. These findings may emphasize that tumor angiogenesis is a process requiring a higher amount of angiogenic factors for its induction than maintenance.