Evidence For Pro Metastatic Role Of Tams Genetic Studies

Evidence for pro-metastatic role of TAMs: Genetic studies in mice have shown decreased rates of tumor growth and metastasis are associated with decreased TAM numbers. Lin and colleagues crossed a transgenic mouse susceptible to mammary cancer with mice containing a recessive null mutation in the CSF-1 gene (Csf1op) and compared tumor progression in wild-type and mice lacking CSF1. Of note, CSF1 is an important survival factor for macrophages. They observed that the absence of CSF-1 significantly reduced lung metastases. However, transgenic expression of CSF-1 in the mammary epithelium of both Csf1op/Csf1op and wild-type tumor-prone mice led to accelerated disease progression and to a significant increase in lung metastasis, which was associated with an enhanced infiltration of TAMs into the primary tumor. In this mouse model, they also observed that TAMs play a crucial role in the ‘‘angiogenic switch† when hyperplastic lesions develop into early stage mammary carcin omas. Similarly, in another study using transplanted tumors, CSF1 depletion resulted in an impairment of tumor growth accompanied with extensive necrosis and poor vascularization, which could be reversed by treatment of mice with CSF1 (Nowicki). These studies provide strong evidence that TAMs promote malignant tumor progression. TAMs promote cancer cell invasion and intravasation: The mechanisms by which TAMs promote metastases are numerous. TAMs have been called the â€Å"jack-of all trades† of the myeloid lineageShow MoreRelatedPrevention And Treatment Of Breast Cancer3159 Words   |  13 Pagesand progression may be directly associated with immunosuppressive factors. On account of an expansion or increase of activation in CD8+ T cells and inhibition or decrease in myeloid-derived suppressor cells (MDSCs), the tumor associated macrophages (TAMs) may allow for immune suppression in breast cancer patients. In a similar manner, standard immunotherapy and checkpoint blockade brings about an optimal clinical response in the regulation of immunity. Scientific research and publications regardingRead MoreResearch Proposal: The role of perivascular macrophages in breast cancer metastasis. 1. Specific2800 Words   |  12 PagesResearch Proposal: The role of perivascular macrophages in breast cancer metastasis. 1. Specific Aims The tumour microenvironment is comprised of both malignant and non-malignant cells. Increasing evidence suggests that the fate of malignant cells is altered by the behaviour of the surrounding nonmalignant cells. Together, the diverse composition of the microenvironment, including immune cell infiltration, stromal cells and extracellular matrix, as well as nutrient and oxygen supply, shape the fateRead MoreCollective Behavior And Stigmergy Of Cancer Cells6661 Words   |  27 Pagesdependence of the correlation function differed completely from the theoretical predictions of standard models of moving particles with mechanisms of local alignment. We propose an explanation for this unexpected finding, supported by an analysis of the role of density in the ability of cells to communicate through the micro-environment (stigmergy), which revealed the emergence of a network-like structure of trails when the system density was sufficiently low. 1 Introduction modelling, driven by the massive