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Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats

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Abstract

We have previously reported sex- and estrous-related differences in hostresistance to the metastatic development of a mammary adenocarcinoma cellline, MADB106, in the Fischer 344 (F344) rat. In other studies, we foundthat surgery suppressed natural killer (NK) cell activity and increased theNK-sensitive metastatic development of MADB106 tumor cells. The currentstudy was designed to explore whether sex or estrous phase at the time ofsurgery impacts the degree of such deleterious effects of surgery. Suchestrous effects could be related to an ongoing clinical debate regarding theimportance of the timing of breast cancer surgery with the menstrual cyclein premenopausal women. Mature F344 males and cycling females underwenteither experimental laparotomy with halothane anesthesia, halothaneanesthesia alone, or were untreated. Five hours after surgery, animalseither were injected with radiolabeled MADB106 tumor cells and assessed forlung tumor cell retention 12 hours later, or underwent blood withdrawal forin vitro assessment of NK cell activity. MADB106 tumor cells metastasizeonly to the lungs, and lung tumor cell retention is: a) an early indicatorof the number of metastases that would develop weeks later, and b) highlysensitive to in vivo levels of NK activity. This mammary adenocarcinoma cellline is syngeneic to the inbred F344 strain of rats used in our studies,thus constituting a model for breast cancer metastasis. The resultsindicated that sex, estrous phase, and surgery interacted in their effectson NK cell activity and tumor metastasis. MADB106 lung tumor cell retentionwas increased by surgery in both sexes (2- to 3-fold) compared to theanesthesia only and control groups. This increase, however, wassignificantly greater in proestrus/estrus (P/E) females than inmetestrus/diestrus (M/D) females. Among the control animals, females in P/Eexhibited significantly less NK cytotoxic activity compared to the males,and the NK activity exhibited by females in M/D was between these twogroups. Surgery suppressed NK cytotoxic activity to a similar level in allgroups. Possible implications of these findings for the surgical care ofwomen with breast cancer are discussed.

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Page, G.G., Ben-Eliyahu, S. Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats. Breast Cancer Res Treat 45, 159–167 (1997). https://doi.org/10.1023/A:1005826403235

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