SFB 832: Molecular Basis and Modulation of Cellular Interactions in the Tumour Microenvironment

越来越多的证据表明，癌症的许多特征不能追溯到单个癌细胞及其携带的基因。最近发现，癌症是一种叫做肿瘤的复杂组织的疾病。这一概念意味着肿瘤的生长不仅由恶性癌细胞决定，还由肿瘤微环境决定。微环境由不同的非癌细胞、细胞外基质和可溶性分子组成。这些成分创造了一个支持癌细胞存活的环境，并负责临床可见肿瘤的形成。在肿瘤微环境中发现的细胞类型包括内皮细胞及其前体、周细胞、平滑肌细胞、各种表型的成纤维细胞和血细胞。在血细胞中有免疫系统的细胞，包括粒细胞、肥大细胞、淋巴细胞和抗原呈递细胞，如巨噬细胞或树突状细胞，目的是识别和消除健康生物体中的肿瘤细胞。与大量关于导致癌细胞永生和恶性转化的主要遗传事件的知识相比，形成肿瘤微环境的精确分子机制知之甚少。这也适用于缺失的免疫识别和排斥肿瘤组织通过免疫细胞。该合作研究中心旨在通过阐明癌细胞与其微环境的分子相互作用的一些关键机制，为这一新兴领域做出重大贡献。合作研究中心将专注于两个主要领域，并研究：(1)与健康组织相比，肿瘤组织中细胞结构、分化和运动方面的分子变化；(2)肿瘤微环境中细胞之间的相互作用和交流（“分子对话”），形成临床明显的肿瘤。此外，在关注微环境的免疫组成的实验中，将评估炎症过程在致癌作用中的作用。从长远的角度来看，合作研究中心的建议旨在提供新的靶点，这对开发新的治疗方法有很大的希望。

There is increasing evidence that many of the traits of cancer could not be traced back to individual cancer cells and the genes they carry. Recently it turned up that cancer is a disease of complex tissues called tumours. This concept implies that tumour growth is not determined only by malignant cancer cells, but also by the tumour microenvironment. The microenvironment consists of different non-cancer cells, extracellular matrix and soluble molecules. These components create a milieu that supports the survival of cancer cells and is responsible for the formation of the clinically visible tumour. Cell types found in the microenvironment of tumours include endothelial cells and their precursors, pericytes, smooth-muscle cells, fibroblasts of various phenotypes and blood cells. Among the blood cells are the cells of the immune system including granulocytes, mast cells, lymphocytes and antigen presenting cells such as macrophages or dendritic cells, destined for the recognition and elimination of tumour cells in healthy organisms. In contrast to a huge body of knowledge on the mostly genetic events that lead to the immortalisation and malignant transformation of the cancer cells, the precise molecular mechanisms shaping the tumour microenvironment are poorly understood. This applies also to the missing immunological recognition and rejection of the tumour tissue through the immune cells. This Collaborative Research Centre aims to make a significant contribution to this arising field by elucidating some key mechanisms that define the molecular interactions of cancer cells with their microenvironment. The Collaborative Research Centre will focus on two major areas and examine: (1) the molecular changes occurring in cell architecture, differentiation and motility within the tumour tissue in comparison to the healthy tissue; (2) the interactions and communication among the cells within the tumour microenvironment ("molecular dialogue") that shapes the formation of a clinically apparent tumour. Moreover, in experiments focussing on the immunological composition of the microenvironment, the role of inflammatory processes for carcinogenesis will be evaluated. As a long-term perspective, the Collaborative Research Centre proposal is aimed at providing novel targets, which hold great promise for the development of novel therapeutics.