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Tumour-Associated Macrophages Case Study

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2.3.5. Tumour-associated macrophages

Macrophages are inherently plastic cells, and this adaptability can be exploited by the tumor to elicit distinct functions at different stages of tumor progression. Less information is available about the complexity of individual macrophage activities and their associated molecular profiles in cancer. Many subpopulations of TAMs exist within a tumor, which probably change temporally during tumor development and geographically depending upon of their location within the tumor micro-environment. For example, TAMs recruited to hypoxic areas promote tumour angiogenesis, whereas TAMs at the tumor–stroma border play an active part in invasion and angiogenesis.
TAMs produce epidermal growth factor (EGF) that
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Association of cancer cells with TAMs throughout the tumour significantly increases their motility, this gets further amplified when cancer cells are found in close proximity to perivascular TAMs. Moreover, cancer cells were observed to invade blood vessels only where perivascular TAMs were located.
Reduction in macrophage infiltration, lead to concomitant decrease in circulating cancer cells. In addition, the EGF–CSF paracrine loop is also important for intravasation, as blocking either signaling pathway lead to a significant reduction in the number of blood-borne cancer cells. Cancer cells and macrophages also use collagen fibres as tram lines to rapidly travel through the stroma. Many of these fibres are tethered to blood vessels, resulting in cancer cells accumulating at these vessels. The density of these fibres is regulated by macrophages, at least during development. (Joyce & Pollard, 2009), (Hanahan & Weinberg, 2011)

2.3.6. Cancer Cells and Cancer Stem Cells
Recent studies suggest that many tumors are heterogeneous containing a pool of clonal subpopulations of Cancer cells and cancer stem cells (CSCs). These tumors contain regions demarcated by various degrees of differentiation, proliferation, vascularity, inflammation, and/or invasiveness; pointing to the existence of a new dimension of
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