Tumor Growth Inhibitory and Natural Suppressor Activities of Murine Bone Marrow Cells: A Comparative Study

Селедцов, В. И.; Taraban, Vadim Y.; Селедцова, Г. В.; Самарин, Д. М.; Avdeev, Ilias V.; Senyukov, Vladimir; Козлов, В. А.

doi:10.1006/cimm.1997.1218

Cited by 8 publications

(7 citation statements)

References 21 publications

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“…Finally, another condition in which natural suppressor cells are expanded is in the late stages of tumor development (16,(53)(54)(55), probably due to stimulation of myelopoiesis in tumor bearers (56,57). Thus, tumor-induced natural suppressor cells might potentially inhibit tumor cell growth, as described for those suppressor cells found in normal bone marrow (17,18) or like those shown here. Hence, natural suppressor cells with features of early myeloid cells are found infiltrating progressively growing tumors, associated with impaired antitumor responses (54,58).…”

Section: Discussionsupporting

confidence: 66%

“…Natural suppression is defined functionally because of its strong inhibition of lymphoproliferative responses (13)(14)(15)(16). However, it may also inhibit the proliferation of other cell types, including those of tumor origin (17,18). In most instances this suppressor activity is nonconstitutive, but is induced upon proper cell activation (19).…”

Section: Yclophosphamide (Cy)mentioning

confidence: 99%

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Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

Peláez

Campillo

López-Asenjo

et al. 2001

The Journal of Immunology

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Adoptive immunotherapy with cyclophosphamide (Cy) increases the host resistance against tumor growth. The precise mechanism(s) by which this therapy enhances tumor suppression is unclear. Cy induces the development of early myeloid cells that may be strongly antiproliferative through NO production. These cells are similar to the natural suppressor cells found in normal bone marrow with a potential antitumor effect. Here we have addressed whether the development of NO-producing cells may be involved in this tumor resistance in Cy-treated mice. The results show a synergism between Cy treatment and tumor-specific lymphocytes transferred systemically (i.v.) or locally (Winn’s assay) that results in a strong tumor suppression. Inhibition of NO production by NG-monomethyl-l-arginine at the site of tumor inoculation results in a loss of the protection achieved by the combined therapy. Cy-treated mice develop splenic early myeloid (CD11b, Gr-1, CD31 (ER-MP12), ER-MP20, ER-MP54) cells producing large amounts of NO upon T cell-derived signals (IFN-γ plus CD40 ligation) able to inhibit tumor cell growth in vitro. Early myeloid cells (ER-MP54+) and cells expressing inducible NO synthase are increased at the site of tumor challenge in mice treated with the combined therapy, but not in those treated with Cy or immune cell transfer alone. Thus, Cy induces the expansion of early myeloid cells, inhibiting tumor cell growth by a mechanism involving NO. Both the recruitment and the activation of these myeloid cells at the site of tumor challenge appear to be dependent on the presence of tumor-specific lymphocytes.

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Section: Discussionsupporting

confidence: 66%

Section: Yclophosphamide (Cy)mentioning

confidence: 99%

Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

Peláez

Campillo

López-Asenjo

et al. 2001

The Journal of Immunology

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“…Therefore, it seems unlikely that the antitumor effect is related to any activation of a specific immune response. Unseparated BM cells have also been reported to inhibit tumor growth by a mechanism involving cell-to-cell interaction [19]. We cannot exclude that this type of mechanism occurred in our in vivo experiments.…”

Section: Discussionmentioning

confidence: 77%

Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice

Maestroni¹,

Hertens²,

Galli³

1999

Cellular and Molecular Life Sciences (CMLS)

130

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Bone marrow stroma produces positive and negative growth regulators which constitute the hematopoietic microenvironment. As many tumors metastasize to the bones, these regulators may also influence tumor growth. Hematopoietic cytokines may indeed exert both positive and negative effect on tumor growth. We report that, when mixed with tumor cells. adherent bone marrow cells inhibit primary tumor growth and metastases formation in mice transplanted with Lewis lung carcinoma or B16 melanoma. Peritoneal macrophages or lymph node cells did not exert any influence. The tumor inhibition was apparently due to soluble factor(s) released by marrow stromal cells. In cocultures with B16 melanoma cells, adherent bone marrow cells exerted a significant antiproliferative effect which was increased by previous culture of the bone marrow cells with granulocyte-macrophage colony-stimulating factor but not with macrophage colony-stimulating factor. Neither neutralizing antibodies against tumor necrosis factor-alpha, transforming growth factor-beta or interferon alpha/beta nor addition of Escherichia coli lipopolysaccharide to generate inflammatory cytokines could affect the antiproliferative effect of bone marrow stromal cells. The bone marrow stroma factor(s) which inhibit tumor growth might, therefore, be a novel growth regulator.

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“…[7,8,13]), but little is known about mediators of antitumor activity. There are only few reports that this activity does no depend on NO [1,11]. The mechanism of induction of immunosuppressor activity in bone marrow NSC is well described, but there are no data about approaches to activation of the antitumor effects.…”

mentioning

confidence: 99%

Mechanism of Antitumor Activity of Bone Marrow Natural Suppressor Cells

Bel'skii¹,

Patrushev²,

Bel'skaya³

et al. 2005

Bull Exp Biol Med

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Co-culturing of P-815 tumor cell strain and intact mouse bone marrow cells nonadherent to plastic resulted in the appearance of soluble mediators with antitumor activity. Bone marrow cells start releasing these antiproliferative factors only after signal exchange with the target tumor cells. The cell-cell contact is an important factor for the induction of antitumor activity. Antitumor activity of bone marrow cells (similarly as immunosuppressive activity) is realized through suppressor factors; the appearance of these factors is induced by target tumor cells.

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Tumor Growth Inhibitory and Natural Suppressor Activities of Murine Bone Marrow Cells: A Comparative Study

Cited by 8 publications

References 21 publications

Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism

Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice

Mechanism of Antitumor Activity of Bone Marrow Natural Suppressor Cells

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