Role of Nk Cells in Rapid in Vivo Clearance of Radiolabeled Tumor Cells

Riccardi, C; Santoni, Angela; Barlozzari, Teresa

doi:10.1016/b978-0-12-341350-5.50089-x

Cited by 8 publications

(7 citation statements)

References 13 publications

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“…Figure l b shows the reconstitution kinetics of splenic NK activity as measured by the in vitro 4-hr 'Cr-release assay against YAC-1 target cells (Herberman et al, 1974). The data in Figure 1 confirm our previous observations that 4 days after LI there is a significant decrease in both in vivo and in vitro NK activity (Riccardi et al, , 1979(Riccardi et al, , 1980. The NK activity was progressively reconstituted in the mice injected with syngeneic BM, reaching the levels of untreated controls on day 12 after LI and BM graft.…”

Section: Assay For Suppressor Cell Activitysupporting

confidence: 87%

Generation of mouse natural killer (NK) cell activity: Effect of interleukin‐2 (IL‐2) and interferon (IFN) on the in vivo development of natural killer cells from bone marrow (BM) progenitor cells

Riccardi

Giampietri

Migliorati

et al. 1986

Intl Journal of Cancer

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The possible effect of IL-2, alpha,beta-IFN and poly I:C (an IFN inducer) administration on the generation of NK cells of LI and BM-reconstituted animals was investigated. B6D2F1 mice were LI (9.5 Gy) by total-body irradiation and reconstituted by i.v. injection of different doses (ranging from 10(6) to 2 X 10(7)) of syngeneic BM, after which the levels of splenic NK activity were evaluated on days 4, 7, 9, 12 and 14 after LI and BM graft. After a marked decline on day 4 (no detectable NK activity at any effector to target ratio tested), NK activity gradually returned, reaching the levels of untreated controls on day 9. Groups of LI and BM-reconstituted mice were also treated i.p. with mouse or human recombinant IL-2 from day 0 through day 3 (15-50 U/day/mouse) after BM transplantation. It appears that an earlier reconstitution of NK activity occurs in IL-2-treated animals as compared to medium-injected controls. LI and BM-reconstituted animals were also treated i.p. with alpha,beta-IFN (10(4) U/mouse) or Poly I:C (1 mg/kg/mouse) from day 0 through day 3, and the splenic NK activity was evaluated at 4, 7, 9, 12 and 14 days after LI and BM graft. Our data indicate that in vivo administration of IFN or Poly I:C was able to cause an earlier maturation of NK activity as measured on days 7 and 9 after LI. In contrast, when the NK activity of IFN-treated animals was compared with that of controls 14 days after LI and BM graft, a significant inhibition was found due to the induction of suppressor cells. Pre-treatment of donor BM with Poly I:C or IFN was also able to induce a more rapid reconstitution of NK activity of recipient mice. The NK activity reconstitution paralleled the increase in the number of splenic LGL. A synergistic effect was obtained when LI mice were transplanted with Poly I:C-pre-treated BM and then treated with IL-2. The effector cell in the IFN and IL-2 treated chimeras is a typical NK cell: asialo GM-1+, Thy 1 +/-, Lyt 1-, Lyt 2- and reactive only against NK-susceptible targets. These data suggest that IL-2 as well as IFN may represent maturational signals in the in vivo physiological regulation of growth and differentiation of BM NK stem-cells.

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Section: Assay For Suppressor Cell Activitysupporting

confidence: 87%

Generation of mouse natural killer (NK) cell activity: Effect of interleukin‐2 (IL‐2) and interferon (IFN) on the in vivo development of natural killer cells from bone marrow (BM) progenitor cells

Riccardi

Giampietri

Migliorati

et al. 1986

Intl Journal of Cancer

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“…Most of the data supporting the significance of NK cells in host resistance against tumors have been obtained from experiments with syngeneic or allogeneic murine tumor-mouse systems [2,3,5,11,16,[26][27][28]33]. The low level of mouse NK cellmediated reactivity against human tumor cells may explain, in part, the results we obtained with the metastatic human tumors.…”

Section: Discussionmentioning

confidence: 88%

“…The expression of metastatic potential of tumor cells in nude mice depends on the experimental protocols, the nature of the tumor cells, and the natural defense mechanisms of the recipient mice. The studies of Hanna and coworkers [5,[11][12][13][14][15][16] and Riccardi et al [26][27][28] suggested that natural killer (NK) cells (high levels are found in nude mice) are particularly efficient in destroying tumor emboli in the circulation. Unlike tumor cells growing in a primary neoplasm, the progenitors of metastases usually circulate in the blood stream as single cells or small cell clumps (homotypic or heterotypic aggregates) and are, therefore, vulnerable to the destructive effects of nonimmune and immune defense mechanisms [6].…”

Section: Introductionmentioning

confidence: 99%

Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice

et al. 1987

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The growth and metastatic behavior of several human tumor lines grown in adult nude mice, nude mice pretreated with antiserum against asialo GM1 glycoprotein, and beige nude mice were studied. The cell lines were all injected s.c. and i.v. A human colon carcinoma line was also injected into the spleen, and two human renal carcinoma lines were injected into renal subcapsule. All the tumor lines grew as fast or faster in adult nude mice compared with beige nude mice. There were no discernible differences in the production of experimental lung metastasis among the three groups of mice, but human colorectal carcinoma cells and human renal carcinoma cells produced more metastases in nude mice than in beige nude mice after intrasplenic or renal subcapsule injection, respectively. In vitro cytotoxicity assays confirmed that adult nude mice had high levels of natural killer (NK) cell activity whereas nude mice pretreated with anti-asialo GM1 serum and beige nude mice did not. The in vitro NK cell activity of nude mice was demonstrable against mouse lymphoma cells but not against human leukemia cells which were sensitive to lysis by human NK cells. These results suggest that the implantation of human tumor cells into beige nude mice, which are deficient in NK cell activity does not provide an advantageous model for the study of growth and metastasis of human neoplasms.

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“…Previous experiments from our laboratory [44--50] and many others [51][52][53][54][55] have suggested that natural killer (NK) cells play a prominent role in host control of hematogenously disseminating tumor cells. These findings prompted us to examine the role that NK cells of nude mice might have in the regulation of metastatic spread of HRCC lines by comparing the metastatic capacity of HRCC cells after injection into adult nude mice (high NK cell activity) and into beige nude mice (low NK cell activity).…”

Section: Growth and Metastasis Of Hrcc Cells In Beige Nude Micementioning

confidence: 99%

Orthotopic implantation is essential for the selection, growth and metastasis of human real cell cancer in nude mice

1990

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Human neoplasms are heterogeneous for a variety of biological properties that include invasion and metastasis. The presence of a small subpopulation of cells with a highly metastatic phenotype has important clinical implications for diagnosis and therapy of cancer. For this reason, it is important to develop an animal model for the selection and isolation of metastatic variants from human neoplasms and for testing the metastatic potential of human tumor cells. We have implanted human renal cell carcinoma (HRCC) cells (obtained from a surgical specimen) into different organs of nude mice and then recovered the tumors and established each in culture. The 5 established lines differed in their biological-metastatic properties and had a unique karyotype, indicating that growth at different organs selects for different subpopulations of HRCC. Moreover, the HRCC did not metastasize unless they were implanted orthotopically. These findings indicate that the appropriate nude mouse model for studying the biology and therapy of HRCC must be based on the orthotopic implantation of tumor cells.

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Role of Nk Cells in Rapid in Vivo Clearance of Radiolabeled Tumor Cells

Cited by 8 publications

References 13 publications

Generation of mouse natural killer (NK) cell activity: Effect of interleukin‐2 (IL‐2) and interferon (IFN) on the in vivo development of natural killer cells from bone marrow (BM) progenitor cells

Generation of mouse natural killer (NK) cell activity: Effect of interleukin‐2 (IL‐2) and interferon (IFN) on the in vivo development of natural killer cells from bone marrow (BM) progenitor cells

Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice

Orthotopic implantation is essential for the selection, growth and metastasis of human real cell cancer in nude mice

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