Stress promotes tumor growth by amplifying the cancer cells’ ability to evade apoptosis

Stress promotes tumor growth by amplifying the cancer cells’ ability to evade apoptosis

A study published in the Journal of Clinical Investigation indicates that stress or the stress hormone adrenaline, through stimulation of beta-adrenoreceptors (ADRs), activate signaling pathways that lead to the inhibition of apoptosis. This enables prostate cancer cells to evade apoptosis, which is an important feature of tumor growth and metastasis.

An increasing body of evidence indicates that psychological stress, i.e., stress hormones and mediators, are involved in the development and progression of cancer – affecting directly or indirectly tumor growth, angiogenesis, and migration or invasion of tumor cells.

Over 25-30 recent studies in this field are discussed only on this reference Website, on which this short news report is published.

A PubMed search, using (“psychological” and “stress”) and “cancer” keywords retrieves overall, 5977 results, 3486 – in the last 10 years; 2046 – in the last 5 years. Thus, more than 30% of all studies relevant to these issues, and reported over the last 4-5 decades, are, in fact, published in the last 5 years.

The ability of tumor cells to evade apoptosis (the process of programmed cell death) is a characteristic hallmark of cancer.

In the Journal of Clinical Investigation study, Sazzad Hassan and colleagues from the Wake Forest University School of Medicine, Winston-Salem, North Carolina demonstrated that in 2 mouse models of prostate cancer – a prostate specific, androgen-dependent transgenic model, and an androgen-independent xenograft model – stress activated the ADRB2/PKA/BAD anti-apoptotic signaling pathway.

Thus, stress may represent a newly defined environmental factor contributing to prostate cancer pathogenesis through an anti-apoptotic signaling pathway that impinges on BCL2-associated death promoter (BAD) phosphorylation. These results are probably the first to establish the critical role of BAD phosphorylation in stress- or adrenaline-induced anti-apoptotic signaling in prostate tumors in vivo.

Importantly, the authors also demonstrate that stress may lead to resistance to anti-androgen (bicalutamide) therapy, an effect they were able to prevent by treatment with an ADRB2 antagonist (a ‘beta-blocker’).

According to the authors, as the prostate cancer diagnosis often increases stress and anxiety levels, the activation of a stress-induced anti-apoptotic pathway may lead to a vicious cycle of stress and cancer progression. The authors also expect that their results could help the identification of biomarkers to predict how a given tumor will respond to stress, and/or distinguish patients’ subgroups that could benefit from stress reduction and pharmacological blockade of stress-induced signaling.

Comments on this study, by a group of experts working on similar issues, are available in the same issue of the Journal of Clinical Investigation (Nagaraja et al., J Clin Invest. 2013; 123:558. doi:10.1172/JCI67887).

More general comments for this study are available on Forbes.com Pharma & Healthcare section.

Source: J Clin Invest, 2013 Jan 25. pii: 63324. doi: 10.1172/JCI63324. [Epub ahead of print]

Read more

Source: Cover Image: A vicious circle of stress signaling in prostate cancer (Figure 9). From: Behavioral stress accelerates prostate cancer development in mice. J Clin Invest. 2013;123(2):874–886. doi:10.1172/JCI63324. Public domain.

You must be logged in to post a comment Login