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Hypoxia and the Hallmarks of Cancer: Angiogenesis and Metastasis

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The following was provided by HypOxygen, our distributor of Hypoxic Workstations in the US

Hanahan and Weinberg’s “Hallmarks of Cancer” are at the root of the multi-step progression of cancer, and they are all influenced by hypoxia in the tumor microenvironment. In this mini-review series, HypOxygen has been taking a closer look at the way Hypoxystation users worldwide are delineating the effects of hypoxia on the Hallmarks of Cancer: so far, we’ve showcased Avoiding Immune Destruction and Tumor Promoting Inflammation and Genome Instability and Mutation and Enabling Replicative Immortality.

In the Hypoxystation, researchers working with cells in culture can mimic the physiological conditions that produce those characteristic Hallmarks. The Hypoxystation enables glove-less access to cultivate and manipulate cells under physiological conditions, in a HEPA-clean environment. Oxygen levels in the Hypoxystation can be reliably and accurately adjusted to below 1%, reflecting the high metabolism, low perfusion tumor microenvironment.

 

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1. Inducing Angiogenesis

Angiogenesis and tumor-associated neo-vascularization are central to the progression of cancer, and hypoxia in the fast-growing, poorly perfused tumor setting is one of the main factors driving the formation of new vessels. Hypoxia in the tumor activates the hypoxia stress response, which is mediated at the cellular level by HIF, VEGF and many other cytokines, growth factors and guidance molecules. As a consequence, endothelial cells and pericytes proliferate and form new blood vessels, which are, however, disorderly and leaky, in turn exacerbating hypoxia in the tumor. Cancer treatment strategies striving to normalize tumor vessels for the purpose of improved drug delivery and alleviation of hypoxia in the tumor are showing great promise.

AngiogenesisSliceLITERATURE:

2. Activating Invasion and Metastasis

As with the other Hallmarks of Cancer, metastasis and cancer progression are correlated with low oxygen levels in the tumor. HIF’s activate the expression of more than 1000 genes, numerous of which play a role in inducing genes involved in the EMT, through direct interactions with HRE’s at promotor sites and other mechanisms such as epigenetic alterations, like methylation/demethylation. Hypoxia promotes migration and invasion by facilitating the endothelial-mesenchymal transition, altering cell-cell contacts, and reducing adhesion to the extra-cellular matrix. Cancer cells and neighboring cells such as fibroblasts are all influenced by hypoxia, and all contribute to the restructuring of the tumor microenvironment. The effects of the Hallmarks of Cancer continually perturb and promote each other, as when hypoxia-driven metabolic reprogramming causes acidification of the extracellular microenvironment through increased production and secretion of lactate, in turn augmenting ECM remodeling and immune evasion. Similarly, formation of novel blood vessels enables extravasation and migration of cancer cells to form new tumors.

MetastasisSliceLITERATURE:


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