Myeloid Vascular Endothelial Growth Factor Expression & its Role in Tumorigenesis

描述(由申请人提供)：我们已经发现髓系细胞中血管内皮生长因子-A表达的缺失在乳腺癌小鼠模型中具有深远和意想不到的影响。我们最近的发现阐明了炎症细胞如何在肿瘤中诱导血管变化，以及这些变化如何改变肿瘤的血流和氧合，以及肿瘤细胞的存活和恶性进展。本文提出的工作将使我们能够探索和利用这些新的和新的发现，以便：确定肿瘤血管生成过程中髓系细胞与内皮细胞相互作用的机制；更好地了解髓系细胞VEGF表达与转移的关系；以及确定这些发现如何用于提高化疗效果。我们提出进一步理解这些现象的目的是：1：确定肿瘤中通过先天免疫细胞分化的血管内皮生长因子信号的分子机制。2：确定髓系细胞中血管内皮生长因子的表达对转移的影响。3：确定来自髓系细胞的血管内皮生长因子如何影响化疗的传递和疗效。总之，我们相信这一应用将解决围绕炎症、血管生成和肿瘤生长过程的关键问题，并特别强调这些过程如何影响乳腺肿瘤的发生和转移。

DESCRIPTION (provided by applicant): We have found that loss of Vascular Endothelial Growth Factor-A expression in myeloid cells has profound and unexpected effects in a mouse model of breast cancer. Our recent findings illustrate how inflammatory cells act to induce vascular changes in tumors, and how these changes alter tumor perfusion and oxygenation, as well as tumor cell survival and malignant progression. The work proposed here will allow us to explore and exploit these new and novel findings, in order to: determine the mechanisms of myeloid cell interactions with endothelial cells during tumor angiogenesis; better understand the relationship between myeloid cell VEGF expression and metastasis; and determine how these findings could be used to increase the efficacy of chemotherapy. The aims we propose to further our understanding of these phenomena are: 1: Determine the molecular mechanisms for differential VEGF signaling through innate immune cells in tumors. 2: Determine how VEGF expression from myeloid cells impacts metastasis. 3: Determine how VEGF from myeloid cells impacts chemotherapy delivery and efficacy. In sum, we believe this application will address key questions surrounding the processes of inflammation, angiogenesis, and tumor growth, with a particular emphasis on how these influence mammary tumorigenesis and metastasis.