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Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination

Ecoclimber

Senior Member
Messages
1,011

Must be taken in context as mouse models do not necessarily translate well into human vivo research.

Genomic responses in mouse models poorly mimic human inflammatory diseases
Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination


Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape.

We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling
in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer.

These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.


Summation:
The results, however, also showed that while adrenaline clearly acted through specific cell receptors, certain drugs can be used to block the pathways at work.

They used a drug known as propranolol to block adrenaline’s action in the stressed mice and regulate lymphatic function to prevent cancer cell spread. This medication is a beta blocker, widely used at present for treating hypertension.

The team looked at data from almost 1,000 breast cancer patients in Italy, analyzing whether their beta-blocker intake had any impact on their risk of metastasis.

When tracked over about seven years, it turned out that those that had been taking beta-blockers also showed far less evidence of tumor cells moving into the lymph nodes and then disseminating to other organs like the lung