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

Gayle Giboney Page, Shamgar Ben-Eliyahu

Research output: Contribution to journalArticle

Abstract

We have previously reported sex- and estrous-related differences in host 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 cells. The current study was designed to explore whether sex or estrous phase at the time of surgery impacts the degree of such deleterious effects of surgery. Such estrous effects could be related to an ongoing clinical debate regarding the importance of the timing of breast cancer surgery with the menstrual cycle in premenopausal women. Mature F344 males and cycling females underwent either experimental laparotomy with halothane anesthesia, halothane anesthesia alone, or were untreated. Five hours after surgery, animals either were injected with radiolabeled 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 line is syngeneic to the inbred F344 strain of rats used in our studies, thus constituting a model for breast cancer metastasis. The results indicated that sex, estrous phase, and surgery interacted in their effects on NK cell activity and tumor metastasis. MADB106 lung tumor cell retention was increased by surgery in both sexes (2- to 3-fold) compared to the anesthesia only and control groups. This increase, however, was significantly greater in proestrus/estrus (P/E) females than in metestrus/diestrus (M/D) females. Among the control animals, females in P/E exhibited significantly less NK cytotoxic activity compared to the males, and the NK activity exhibited by females in M/D was between these two groups. Surgery suppressed NK cytotoxic activity to a similar level in all groups. Possible implications of these findings for the surgical care of women with breast cancer are discussed.

Original languageEnglish (US)
Pages (from-to)159-167
Number of pages9
JournalBreast Cancer Research and Treatment
Volume45
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Proestrus
Estrus
Natural Killer Cells
Neoplasm Metastasis
Metestrus
Neoplasms
Diestrus
Lung
Anesthesia
Inbred F344 Rats
Halothane
Breast Neoplasms
Adenocarcinoma
Breast
Cell Line
Menstrual Cycle
Laparotomy
Control Groups

Keywords

  • Breast cancer
  • Estrous cycle
  • Metastasis
  • Natural killer cell
  • Rat
  • Surgery

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats. / Page, Gayle Giboney; Ben-Eliyahu, Shamgar.

In: Breast Cancer Research and Treatment, Vol. 45, No. 2, 1997, p. 159-167.

Research output: Contribution to journalArticle

@article{86261d0c495442469b46f3702d1a84d6,
title = "Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats",
abstract = "We have previously reported sex- and estrous-related differences in host 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 cells. The current study was designed to explore whether sex or estrous phase at the time of surgery impacts the degree of such deleterious effects of surgery. Such estrous effects could be related to an ongoing clinical debate regarding the importance of the timing of breast cancer surgery with the menstrual cycle in premenopausal women. Mature F344 males and cycling females underwent either experimental laparotomy with halothane anesthesia, halothane anesthesia alone, or were untreated. Five hours after surgery, animals either were injected with radiolabeled 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 line is syngeneic to the inbred F344 strain of rats used in our studies, thus constituting a model for breast cancer metastasis. The results indicated that sex, estrous phase, and surgery interacted in their effects on NK cell activity and tumor metastasis. MADB106 lung tumor cell retention was increased by surgery in both sexes (2- to 3-fold) compared to the anesthesia only and control groups. This increase, however, was significantly greater in proestrus/estrus (P/E) females than in metestrus/diestrus (M/D) females. Among the control animals, females in P/E exhibited significantly less NK cytotoxic activity compared to the males, and the NK activity exhibited by females in M/D was between these two groups. Surgery suppressed NK cytotoxic activity to a similar level in all groups. Possible implications of these findings for the surgical care of women with breast cancer are discussed.",
keywords = "Breast cancer, Estrous cycle, Metastasis, Natural killer cell, Rat, Surgery",
author = "Page, {Gayle Giboney} and Shamgar Ben-Eliyahu",
year = "1997",
doi = "10.1023/A:1005826403235",
language = "English (US)",
volume = "45",
pages = "159--167",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "2",

}

TY - JOUR

T1 - Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats

AU - Page, Gayle Giboney

AU - Ben-Eliyahu, Shamgar

PY - 1997

Y1 - 1997

N2 - We have previously reported sex- and estrous-related differences in host 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 cells. The current study was designed to explore whether sex or estrous phase at the time of surgery impacts the degree of such deleterious effects of surgery. Such estrous effects could be related to an ongoing clinical debate regarding the importance of the timing of breast cancer surgery with the menstrual cycle in premenopausal women. Mature F344 males and cycling females underwent either experimental laparotomy with halothane anesthesia, halothane anesthesia alone, or were untreated. Five hours after surgery, animals either were injected with radiolabeled 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 line is syngeneic to the inbred F344 strain of rats used in our studies, thus constituting a model for breast cancer metastasis. The results indicated that sex, estrous phase, and surgery interacted in their effects on NK cell activity and tumor metastasis. MADB106 lung tumor cell retention was increased by surgery in both sexes (2- to 3-fold) compared to the anesthesia only and control groups. This increase, however, was significantly greater in proestrus/estrus (P/E) females than in metestrus/diestrus (M/D) females. Among the control animals, females in P/E exhibited significantly less NK cytotoxic activity compared to the males, and the NK activity exhibited by females in M/D was between these two groups. Surgery suppressed NK cytotoxic activity to a similar level in all groups. Possible implications of these findings for the surgical care of women with breast cancer are discussed.

AB - We have previously reported sex- and estrous-related differences in host 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 cells. The current study was designed to explore whether sex or estrous phase at the time of surgery impacts the degree of such deleterious effects of surgery. Such estrous effects could be related to an ongoing clinical debate regarding the importance of the timing of breast cancer surgery with the menstrual cycle in premenopausal women. Mature F344 males and cycling females underwent either experimental laparotomy with halothane anesthesia, halothane anesthesia alone, or were untreated. Five hours after surgery, animals either were injected with radiolabeled 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 line is syngeneic to the inbred F344 strain of rats used in our studies, thus constituting a model for breast cancer metastasis. The results indicated that sex, estrous phase, and surgery interacted in their effects on NK cell activity and tumor metastasis. MADB106 lung tumor cell retention was increased by surgery in both sexes (2- to 3-fold) compared to the anesthesia only and control groups. This increase, however, was significantly greater in proestrus/estrus (P/E) females than in metestrus/diestrus (M/D) females. Among the control animals, females in P/E exhibited significantly less NK cytotoxic activity compared to the males, and the NK activity exhibited by females in M/D was between these two groups. Surgery suppressed NK cytotoxic activity to a similar level in all groups. Possible implications of these findings for the surgical care of women with breast cancer are discussed.

KW - Breast cancer

KW - Estrous cycle

KW - Metastasis

KW - Natural killer cell

KW - Rat

KW - Surgery

UR - http://www.scopus.com/inward/record.url?scp=0030755148&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030755148&partnerID=8YFLogxK

U2 - 10.1023/A:1005826403235

DO - 10.1023/A:1005826403235

M3 - Article

C2 - 9342441

AN - SCOPUS:0030755148

VL - 45

SP - 159

EP - 167

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 2

ER -