Evidence For Pro Metastatic Role Of Tams : Genetic Studies

975 WordsFeb 16, 20164 Pages
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 carcinomas. 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 “jack-of all trades” of the myeloid lineage

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