Stress increases metastatic spread of a mammary tumor in rats: evidence for mediation by the immune system

Brain Behav Immun. 1991 Jun;5(2):193-205. doi: 10.1016/0889-1591(91)90016-4.


Causal relationships among stress, immune suppression, and enhanced tumor development have often been suggested, but direct evidence is scant. We studied stress effects in Fischer 344 rats using a tumor model in which lung metastases of a syngeneic mammary tumor (MADB106) are controlled by natural killer (NK) cells. Animals exposed to acute stress showed a substantial decrease in NK cell cytotoxicity against this tumor in an in vitro assay and, when intravenously injected with this tumor, showed a twofold increase in surface lung metastases. The critical period during which stress increases metastases appears to be the same as that during which this tumor is known to be controlled by NK cells. These findings support the hypothesis that stress can facilitate the metastatic process via suppression of the immune system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / complications
  • Adenocarcinoma / immunology
  • Adenocarcinoma / secondary*
  • Adrenocorticotropic Hormone / blood
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Corticosterone / blood
  • Cytotoxicity, Immunologic
  • Immune Tolerance
  • Immunologic Deficiency Syndromes / etiology
  • Immunologic Deficiency Syndromes / immunology
  • Injections, Intravenous
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology*
  • Lung Neoplasms / complications
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Male
  • Mammary Neoplasms, Experimental / complications
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Neoplasm Transplantation
  • Rats
  • Rats, Inbred F344 / immunology
  • Stress, Physiological / complications
  • Stress, Physiological / immunology*
  • Stress, Physiological / physiopathology
  • Swimming


  • Antibodies, Monoclonal
  • Adrenocorticotropic Hormone
  • Corticosterone