Gg. Page et S. Beneliyahu, INCREASED SURGERY-INDUCED METASTASIS AND SUPPRESSED NATURAL-KILLER-CELL ACTIVITY DURING PROESTRUS ESTRUS IN RATS/, Breast cancer research and treatment, 45(2), 1997, pp. 159-167
We have previously reported sex-and estrous-related differences in hos
t resistance to the metastatic development of a mammary adenocarcinoma
cell line, MADB106, in the Fischer 344 (F344) rat. In other studies,
we found that surgery suppressed natural killer (NK) cell activity and
increased the NK-sensitive metastatic development of MADB106 tumor ce
lls. The current study was designed to explore whether sex or estrous
phase at the time of surgery impacts the degree of such deleterious ef
fects of surgery. Such estrous effects could be related to an ongoing
clinical debate regarding the importance of the timing of breast cance
r surgery with the menstrual cycle in premenopausal women. Mature F344
males and cycling females underwent either experimental laparotomy wi
th halothane anesthesia, halothane anesthesia alone, or were untreated
. Five hours after surgery, animals either were injected with radiolab
eled MADB106 tumor cells and assessed for lung tumor cell retention 12
hours later, or underwent blood withdrawal for in vitro assessment of
NK cell activity. MADB106 tumor cells metastasize only to the lungs,
and lung tumor cell retention is: a) an early indicator of the number
of metastases that would develop weeks later, and b) highly sensitive
to in vivo levels of NK activity. This mammary adenocarcinoma cell lin
e is syngeneic to the inbred F344 strain of rats used in our studies,
thus constituting a model for breast cancer metastasis. The results in
dicated that sex, estrous phase, and surgery interacted in their effec
ts on NK cell activity and tumor metastasis. MADB106 lung tumor cell r
etention was increased by surgery in both sexes (2-to 3-fold) compared
to the anesthesia only and control groups. This increase, however, wa
s significantly greater in proestrus/estrus (P/E) females than in mete
strus/ diestrus (M/D) females. Among the control animals, females in P
IE exhibited significantly less NK cytotoxic activity compared to the
males, and the NK activity exhibited by females in M/D was between the
se two groups. Surgery suppressed NK cytotoxic activity to a similar l
evel in all groups. Possible implications of these findings for the su
rgical care of women with breast cancer are discussed.