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Macrophage-Related Interaction Pathways in Tumor Stroma

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Gusenbauer,  Simone Salome
Ullrich, Axel / Molecular Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Gusenbauer, S. S. (2012). Macrophage-Related Interaction Pathways in Tumor Stroma. PhD Thesis, Technische Universität, München.


Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-E4AC-A
Abstract
Cancer is a leading cause of death in developed countries. Within the adult population, epithelial cancers are—with 83%—the most frequent cancer types (1). The deadliest cancers are in men those of lung, colon and prostate, and in women, those of breast, colon and lung (2). Based on observations in the early twentieth century that some cancers are familial, scientists began to search for genetic changes that might underlie cancer development. Dominant gain-of-function and recessive loss-of-function alterations in critical gatekeeper genes, e.g., oncogenes and tumor-suppressor genes, have been identified and characterized during the last decades. Tumorigenesis is now recognized as a multistep process during which cancer cells accumulate multiple and sequential genetic alterations affecting intrinsic cellular programs, such as cell proliferation, cell death, differentiation, metabolism, and cell adhesion (3, 4). During the last two decades it has been increasingly recognized that the surrounding tissue, or so-called tumor stroma, plays an important part in neoplastic growth (5, 6). Thus, tumors are regarded as complex organs consisting of two distinct but interdependent compartments: the tumor epithelial cells themselves and the stroma in which they disperse. During the neoplastic process somatic genetic alterations occur in both, tumor cells and stromal cells—also referred to as tumor stroma co-evolution (7). Stromal cells are a heterogeneous mixture of different cell lineages. It is believed, that tumorigenesis cannot proceed without active cooperation from the stroma. This cooperation influences tumor establishment, progression and dissemination (5). When viewed from this perspective, the biology of a tumor can only be understood by studying the cancer cells themselves as well as the ‘‘tumor microenvironment’’ that they construct during the multistep tumorigenesis.