Pastor-Pareja José Carlos, Wu Ming, Xu Tian
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06519, USA.
Dis Model Mech. 2008 Sep-Oct;1(2-3):144-54; discussion 153. doi: 10.1242/dmm.000950. Epub 2008 Sep 18.
Studies in mice and humans have demonstrated a role for the immune system in preventing the growth of tumors. Deciphering the mechanisms involved in the immune response to tumors is essential to our understanding of immune recognition and cancer progression. Here we report an innate immune response to tumors in Drosophila melanogaster. We found that circulating blood cells, termed hemocytes, adhere to tumors upon detection of basement membrane disruption, and subsequently counter their growth. Basement membrane components are remarkably conserved throughout the animal kingdom, providing a unique structure for the immune system to sense tissue integrity. Further, we show that tissue damage activates JNK signaling in both tumors and aseptic wounds, causing expression of JAK/STAT-activating cytokines. Cytokine secretion from the injured tissue is amplified into a systemic response through the induction of additional cytokine expression in the hemocytes and the fat body, resulting in hemocyte proliferation. Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans.
对小鼠和人类的研究表明,免疫系统在抑制肿瘤生长中发挥作用。破解肿瘤免疫反应所涉及的机制对于我们理解免疫识别和癌症进展至关重要。在此,我们报告了黑腹果蝇对肿瘤的先天性免疫反应。我们发现,被称为血细胞的循环血细胞在检测到基底膜破坏后会附着于肿瘤,并随后对抗其生长。基底膜成分在整个动物界都非常保守,为免疫系统感知组织完整性提供了独特的结构。此外,我们表明组织损伤会激活肿瘤和无菌伤口中的JNK信号通路,导致JAK/STAT激活细胞因子的表达。通过诱导血细胞和脂肪体中额外的细胞因子表达,受伤组织的细胞因子分泌被放大为全身性反应,从而导致血细胞增殖。我们的发现揭示了果蝇对肿瘤和伤口反应中的共同机制。类似的先天性反应可能是脊椎动物和人类对肿瘤和组织损伤反应的基础。