Tina Haliotis

Organization of a repetitive human 1.8 kb KpnI sequence localized in the heterochromatin of chromosome 15

We have isolated a repetitive 1.8 kb Kpnl DNA sequence which is amplified in the homogeneously staining regions of a human melanoma cell line. Under low stringency conditions this sequence (D15Z1) hybridized in situ to the centromeric heterochromatin of chromosomes 1, 9, 15p, 16, and distal Yq as well as to the the short arms of the other acrocentric chromosomes. Under conditions of high stringency, labelling was predominantly on the short arm of chromosome 15. D15Z1 was shown to be present at approximately 3,000 copies per haploid genome and organized in long tandem arrays showing restriction site heterogeneity. Sequences homologous to D15Z1 were highly enriched in the less dense shoulder region of a Ag+—Cs2SO4 gradient. Analysis of D15Z1 indicated that this sequence is composed of tandemly arranged imperfect repeats of the consensus 5′ AATGG 3′ similar to previously identified satellite III sequences. Digestion of D15Z1 with HinfI resulted in a series of restriction fragments making up a subset of the HinfI ladder components of satellites III and IV. These data suggest that D15Z1 represents a chromosome 15 specific domain of human satellites III or IV and that it makes up the major fraction of the heterochromatin of this chromosome. Possible relationships between this sequence and the cytochemical staining properties of human chromosomes with distamycin A/DAPI, D280/170, and antiserum to 5-methylcytosine are discussed.

Do NK cells play a role in anti-tumor surveillance?

A class of lymphocytes found in several mammalian species including man will kill cells of many tumor lines invitro(1-4). There is growing evidence, derived mainly from the work of Kiessling and co-workers, that these natural killer (NK) cells play a role in surveillance against tumor developmentin vivo. In this article John Roder and Tina Haliotis discuss a hypothesis for anti-tumor surveillance which integrates all of the potentially important immunological systems in the host and gives to NK cells the role of foremost barrier against developing tumors.

Tumor cell differentiation modulates susceptibility to natural killer cells

Abstract Induced differentiation in three human cell lines altered their sensitivity specifically to human natural killer (NK) cells by affecting their expression of NK target antigens. Differentiation of HL-60, a promyelocytic leukemia cell line, and the erythroleukemic cell line K562 was accompanied by a concomitant decrease in susceptibility to NK-mediated lysis whereas induction of MeWo melanoma cells resulted in an enhanced sensitivity to lysis. Our findings suggest that target cell susceptibility to NK-mediated lysis may in part be dependent on the stage of differentiation of the tumor cell target.

EVIDENCE FOR IN VIVO NK REACTIVITY AGAINST PRIMARY TUMORS

Publisher Summary This chapter presents evidence for in vivo natural killer (NK) reactivity against primary tumors. There is strong evidence that NK cells play a role in protection against the growth and metastasis of transplantable tumors. There is, however, little evidence that NK cells play a protective role against the development of primary tumors. One of the important evidences on this topic is that aging mice (> 6 months) have diminished NK function and also exhibit an increased incidence of spontaneous tumors. In one study described in the chapter, raised in vitro NK activity against YAC or syngeneic, MCA-induced fibrosarcomas in mice deprived of B cells by chronic anti-μ treatment correlated well with an increased resistance to induction of primary tumors by MCA. An important control in these studies was the observation that the incidence and growth-rate of progressing tumors induced by Moloney sarcoma virus (MSV) did not differ in anti-μ-suppressed or normal control mice that were untreated with normal gammaglobulin. Because host defense in the MSV system is clearly Tcell-dependent, this indicates that B cell-deprived mice have normal T function and augmented NK activity does not influence a T-cell-dependent rejection system.

SPECIFICITY OF NATURAL KILLER (NK) CELLS: NATURE OF TARGET CELL STRUCTURES

Publisher Summary This chapter discusses the specificity of natural killer cells and nature of target cell structures. NK cells have now demonstrated the killing of a wide variety of malignant cells and some normal cells to a lesser extent without any apparent need for prior stimulation. Studies using unlabelled targets in cross competition assays with a panel of Cr labeled target cells have shown that cytotoxicity could be inhibited by some but not all target cells. Those cells most sensitive to NK lysis proved to be the best competitors, and a good correlation was found between susceptibility to direct lysis and competition among a variety of targets. The ability of different cell lines to compete inferred but did not prove the existence of cross reacting target antigens and a complementary receptor on the effector cell. The studies on human target cell lines have demonstrated the presence of neutral 140,000 d glycoproteins which inhibited NK but not antibody-dependent cellular cytotoxicity. Similar structures were not found in supernatants of NK-resistant cell lines. The results from both murine and human systems demonstrate that glycoproteins are effective in inhibiting target cell–effector cell interactions and subsequent cytolysis, suggesting carbohydrate moieties as possible target structures.