Role of NK cells in the control of metastatic spread and growth of tumor cells in mice

Abstract

The ability of BALB/c nude and C57BL/6 mice to eliminate tumor cells from the blood stream was severely impaired after a single inoculation of 0.2 ml of anti-asialo BMI (asGMI) serum, diluted 1:40 to 1:320. The number of i.v.-inoculated YAC-I cells surviving in the lungs of BALB/c nude mice pretreated with anti-asGMI serum was 28 times higher than in the control nude mice. In this respect, nude mice treated with anti-asGMI behaved similarly to beige mice. The increase in the initial survival of tumor cells in the mice that was induced by pre-treatment with anti-asGMI resulted in a substantial increase in the number of artificial lung metastases that developed. In C57BL/6 +/+ mice treated with anti-asGMI and in C57BL/6 beige mice, i.v. inoculation of B16 melanoma cells induced 10 times more metastatic foci in the lungs than in the control C57BL/6 +/+ mice. In contrast, in nude mice which possess higher levels of NK reactivity, metastatic growth was suppressed 7-fold in comparison with intact C57BL/6 +/+ mice. In beige mice and in C57BL/6 +/+ mice treated with anti-asGMI, multiple metastatic foci developed in the liver, whereas in control C57BL/6 +/+ and nude mice, no extrapulmonary metastases were found. These data indicate that B16 melanoma cells are able to grow in the liver, but their growth is ordinarily prevented by NK cells. The antimetastatic defense of C57BL/6 mice treated by anti-asGMI could be restored by transplantation of 40 X 10(6) normal spleen cells. This antimetastatic effect of transplanted spleen cells was mediated by asGMI-bearing cells, since after in vitro pre-treatment of normal spleen cells with anti-asGMI and complement, they lost their ability to inhibit the development of artificial metastases in the lungs of C57BL/6 mice. Suppression of NK reactivity by multiple injections of anti-asGMI (every 4 to 5 days), in C57BL/6 mice inoculated intrafootpad (i.f.p.) with B16 melanoma or 3LL tumor cells, did not influence the growth of local tumors, but dramatically accelerated the development of spontaneous pulmonary metastases. These data demonstrate that NK cells may play an important role in resistance to the dissemination of tumor cells, and therefore contribute to the control of metastasis formation in mice.

Severe pulmonary metastasis in obese and diabetic mice

“…22 During the early phase of metastasis, cancer cells are recognized and destroyed by the host's immune system, especially by NK cells. 23,24 Therefore, we have focused on NK cell function in obesity-promoted metastasis. Splenic NK cell numbers were decreased in db/db and ob/ob mice, and 2-week leptin replacement in ob/ob mice recovered NK cell numbers to the level in wild-type mice.…”

Increased emotional distress in daughters of breast cancer patients is associated with decreased natural cytotoxic activity, elevated levels of stress hormones and decreased secretion of Th1 cytokines

“…21,37 Although the association between impaired NCA and the development of breast cancer has not been established, research on humans and other species points to a significant role of NCA in preventing the development of cancer, including breast cancer, and its metastases. [1][2][3][4]8,9 Additional studies doc- norepinephrine levels and state anxiety, (d) IL-2-induced NCA and emotion-focused coping, (e) IL-2-induced NCA and problem-focused coping, (f) IL-2-induced NCA and perceived control, (g) norepinephrine levels vs. perceived control, (h) IL-2 secretion and perceived control, (i) norepinephrine levels and IL-2-induced NCA and (j) epinephrine levels and IL-2 secretion. In general, correlations are done with data from both DBCP and controls, whereas correlations with perceived control (f-h) are done for DBCP only.…”

Natural killer cells play a critical role in the immune response following immunization with melanoma-antigen-engineered dendritic cells

“…Natural killer cells have been suggested to be important in the metastasis of murine tumors, as beige mice receiving intravenous injection of B16 melanoma developed a 10-fold increase in metastatic foci in the lung compared to wild-type C57BL/6 mice. 48 Studies using DC vaccination in NK-deficient (beige) mice have been quite limited. 28 Our findings of impaired protection to B16 tumor challenge in beige mice following immunization with MART-1-engineered DC further confirm the critical role of NK cells to the generation of an immune response following immunization with genemodified DC.…”