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New Animal Stress Model Links the Stress-Induced T-helper 2 Shift to Colon Cancer Growth

colon cancer and stress

In the October 2013 issue of Biochemical and Biophysical Research Communications, Ni Hou and colleagues from the Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi, China, demonstrated that a novel form of sound stress induced a T helper (Th)2 shift and that this is related to colon cancer progression in mice.

Numerous epidemiological reports indicate a connection between stress and cancer.

For example, data related to a Finnish twin cohort study or the Chinese Cultural Revolution suggests a link between stressful life events and cancer.

Furthermore, fundamental and clinical studies demonstrate that psychological stress and other biobehavioral factors may contribute to cancer onset and progression. For instance, breast cancer, ovarian cancer, leukemia and prostate cancer have been linked to stress, stress hormones or sympathetic innervation.

T helper (Th)1 immunity is considered a major defense mechanism in immunosurveillance related to tumor development. A profound Th2 shift linked to a deficiency of IL-12, and overproduction of IL-10 and TGF-β seems to play an inappropriate immunosuppressive role, allowing increased tumor growth (Chouaib, S et al., Immunol. Today, 1997, 18:493).

In addition, stress is a potent inducer of Th2 shift, and both glucocorticoids and catecholamines upregulate the immunosuppressive IL-10 (IJ Elenkov & GP Chrousos, Trends Endocrinol Metab, 1999, 10:359), while stress may restrain the immunostimulatory effects of interleukin-12. Thus, stress-hormone-induced suppression of cellular immunity might contribute to increased growth of certain tumors.

Animal models have been often used to study these interactions.

In fact, two reports in Science magazine, using mice subjected to inescapable shock were perhaps the first to document a link between experimental stress and tumor growth (Sklar LS & Anisman H, Science, 1979, 205:513; Visintainer MA et al., Science. 1982, 216:437).

In the Biochemical and Biophysical Research Communications study, Ni Hou et al. report that mice exposed to a chronic scream sound stress (frequencies from 0.5 kHz to 4 kHz; 6 h daily for 2 weeks), when compared to control animals, had enlarged adrenal cortex zona fasciculata, and increased serum concentrations of norepinephrine (noradrenaline) and corticosterone.

These mice also had lower microarray intensities of serum TNF-α and IL-2 (Th1 cytokines), higher intensities of serum IL-4, IL-5, IL-6, IL-10, and IL-13 (Th2 cytokines), and decreased IFN-γ/IL-4 ratio in tumor infiltrated lymphocytes and tumor microenvironment.

All these neurohormonal-immune changes were associated with morphological alterations indicating colon cancer progression.

These results may suggest that further studies investigating the impact of chronic stress on colon cancer progression are warranted.

Source: Biochem Biophys Res Commun, 2013, 439:471-6. doi:10.1016/j.bbrc.2013.08.101. Epub 2013 Sep 10
Read more: Biochemical and Biophysical Research Communications

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