Impact of Stress Upon Cancer Metastasis, 2010, Moreno-Smith et al

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DigitalDrifter

Senior Member (Voting Rights)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037818/

Abstract
The influence of psychosocial factors on the development and progression of cancer has been a longstanding hypothesis since ancient times. In fact, epidemiological and clinical studies over the past 30 years have provided strong evidence for links between chronic stress, depression and social isolation and cancer progression.

By contrast, there is only limited evidence for the role of these behavioral factors in cancer initiation. Recent cellular and molecular studies have identified specific signaling pathways that impact cancer growth and metastasis. This article provides an overview of the relationship between psychosocial factors, specifically chronic stress, and cancer progression.


Conclusion
In modern lifestyle societies, chronic stress has been associated with the pathogenesis of many diseases, including cancer. Chronic stress results in the activation of specific signaling pathways in cancer cells and the tumor microenvironment, leading to tumor growth and progression. Elucidation of these pathways is essential for the development of novel approaches to block the deleterious effects of stress biology on cancer growth and metastasis.
 
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I haven't read this paper yet, just the abstract. The role of cortisol in cancers is something I've been giving some thought to, after a friend said that he thought the stressful job he had when he first became ill might have caused his leukemia.

The title of the following 2018 paper appears at first glance to suggest there might be something in that idea:
Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression, 2018
However, it turns out that this paper isn't evidence that stress or even cortisol causes cancer. It suggests that you have to have the acute myeloid leukaemia cells first, and they use cortisol to induce expression of a receptor that causes some effects that favour the survival of the malignant cells.
The progression of acute myeloid leukemia (AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune surveillance. However, the systemic regulatory mechanisms underlying this phenomenon remain largely unknown. In this study, we discovered a fundamental systemic biochemical strategy that allows AML cells to employ physiological systems within the body to survive and escape immune attack. We found that AML cells use a crucial human adrenal cortex hormone (cortisol) to induce the expression of neuronal receptor latrophilin 1 (LPHN1), which facilitates exocytosis. This receptor interacts with the blood plasma protein fibronectin leucine rich transmembrane protein 3 (FLRT3) to cause secretion of the immune suppressor galectin-9, which impairs the anticancer activities of cytotoxic lymphoid cells.
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It's not so much that 'cortisol causes the cancer'. It seems to be more that leukemia cells increase cortisol levels.
(Leukemia cells cause reduced blood glucose levels > increased CTRH > increased ACTH > increased cortisol)
In the presence of the leukaemia cells, the cortisol up regulates LPHN1, and LPHN1 interacts with FLRT3 to produce galectin-9. And the galectin-9 protects the leukaemia cells from destruction by immune cells.

There seem to be a few links in the chain of events that don't happen if the leukaemia cells aren't there. Cortisol doesn't cause the problems if the leukaemia cells aren't there.

As the authors of the 2018 paper say:
Thus, AML cells [the cancer cells] engage crucial functional systems of the human body to support their survival and attenuate the anticancer activities of cytotoxic lymphoid cells [the immune cells].
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That's something I think we have to remember. Everyone has cortisol, pretty much everyone has stress. Not everyone gets leukaemia.
And higher levels of cortisol once you have cancer don't necessarily mean you are a high-stress person causing the progression of your cancer - the cancer can increase the level of cortisol. The causality seems to be in the opposite direction from the prevailing view of stress causing cancer.


I don't want to rule out the possibility that someone who is very stressed might have a higher chance of becoming ill. Every gardener knows how plants stressed by a lack of water are far more likely to suffer from diseases than plants that are well-watered and well-nourished. And a stressed person might not sleep well, might not eat well, might smoke and drink alcohol. Being very stressed typically isn't fun, and so ideally we'd organise society so people aren't chronically very stressed.

The 2010 paper that is the subject of the thread notes that there isn't much evidence of the behavioural factors of stress, depression and isolation initiating cancers. I actually think that they could do, but mainly via things like smoking, alcohol, bad food and poor sleep.

The 2010 paper seems to be suggesting that there is strong evidence that stress favours cancer progression. I feel quite doubtful that there is some magical BPS link. I think it's more likely to be mostly the mundane and obvious links - things like people who are isolated not having the support structures to get them to their chemotherapy treatments.

As has been mentioned in other threads with respect to ME/CFS, there's a big problem when people start saying patients have caused their disease, or have failed to beat it, because of their neurotic personalities. Or when it's suggested that people can be fixed by doing a mindfulness course and thinking happy thoughts. I don't think we've seen good evidence for those things in cancer at all.
 
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I have low cortisol but that didn't stop me getting breast cancer.

It is interesting to note ( and I don't think I can quite put this into words properly) that having cancer and surviving seems to have changed the opinion medics have of me.

They now treat me with more respect. I saw this first when I was going through treatment. Suddenly I was believed.

I wasn't the stupid , weak, deluded woman after all.

The NHS certainly put me over more stress trying to get a course of cancer treatment I could actually follow. It was extra frightening thanks to them.

However even with that I survived. There were no attempts by the NHS to make the process less stressful.
 
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