Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice

Mantovani, Alberto; Giavazzi, Raffaella; Polentarutti, Nadia; Spreafico, F.; Garattini, Silvio

doi:10.1002/ijc.2910250511

Cited by 57 publications

(19 citation statements)

References 26 publications

(32 reference statements)

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“…It was found that a high macrophage content was related to the low incidence of métastasés in experimental sys tems, although not confirmed by all [5,[10][11][12]. Our results indicate that not only the mononuclear system is impaired in patients with métastasés as was shown by Krishnan et al [6], but there is also a decrease in lym phocyte function to produce the MIF lymphokine which is responsible for macrophage attraction.…”

Section: Mif Testsupporting

confidence: 72%

Sequential Study of Macrophage Migration Inhibition Factor in Renal Cell Carcinoma Patients

Gillon

Livni²,

Servadio³

1988

Eur Urol

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Section: Mif Testsupporting

confidence: 72%

Sequential Study of Macrophage Migration Inhibition Factor in Renal Cell Carcinoma Patients

Gillon

Livni²,

Servadio³

1988

Eur Urol

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“…Macrophages form two of the murine neoplasms used in the present study (mFS6 and MN/MCA1 sarcomas) showed no evidence of activation in terms of enhanced tumoricidal capacity, and they augmented tumor cell proliferation in vitro at least at low effector to target cell ratios, in the same range as those presumably present in vivo at the tumor site (Mantovani, 1981). It has been suggested that TAM may stimulate tumor growth in vivo, at least at the primary tumor site (Evans, 1979;Salmon and Hamburger, 1978;Mantovani et al, 1980;Mantovani, 1981). The results presented here may suggest that tumor-derived chemotactic factor(s) may be one of the mechanisms involved in determining the level of TAM in neoplasms.…”

Section: Discussionmentioning

confidence: 85%

Chemotactic activity for mononuclear phagocytes of culture supernatants from murine and human tumor cells: Evidence for a role in the regulation of the macrophage content of neoplastic tissues

Bottazzi

Polentarutti

Balsari

et al. 1983

Intl Journal of Cancer

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Culture Supernatants from 14 mouse solid tumors, 2 mouse lymphomas, 8 human solid tumor lines and 3 human leukemia-lymphomas were examined for chemotactic activity in blind-well chemotaxis chambers using murine peritoneal macrophages and human blood monocytes as indicator cells. Culture supernatants from various murine and human solid tumors had appreciable chemotactic activity for mononuclear phagocytes. Chemotactic activity was found in murine tumors of different histology and transplantation history, including autochthonous mammary carcinomas and chemically-induced sarcomas. Chemotactic activity was not unique to neoplastic cells because is was detected also in supernatants of two preparations of mouse embryo fibroblasts and two human lung embryo fibroblast lines. Production of tumor-derived chemo-attractants did not require serum in the culture medium, was inhibited by the protein synthesis inhibitor Cycloheximide, but was unaffected by the DNA synthesis inhibitor Mitomycin C. Murine supematants were active on human monocytes and vice-versa. A first preliminary characterization of the chemotactic activity of the human sarcoma line 8387 revealed that it was not dialyzable, that most of the activity was retained at 56' C for 30 min, but not at 100" C, and that it was susceptible to proteolytic enzymes (trypsin and proteinase K) but unaffected by DNase and RNase. Upon fractionation on a Sephadex G-75 column, the activity eluted in a single, relatively broad peak in the cytocrome C region, corresponding to an apparent molecular weight of about 12,000. In the heterogeneous series of murine solid tumors studied, a significant, though far from absolute, correlation ( F 0.7 I, p0.013) was found between chemotactic activity in culture supernatants (expressed as area under the chemotaxis titration curve) and the percentage of tumor-asoociated macrophages. It is suggested that tumor-derived chemotactic factor@) play a role in the regulation of the macrophage content of neoplastic tissues.Macrophages are present in variable proportions in murine and human neoplastic tissues (Evans, 1967(Evans, , 1972Carr, 1977). The mechanism involved in the regulation of the macrophage content of tumors and the in vivo significance of tumor-associated macrophages (TAM) are largely a matter of speculation (Evans, 1979).The levels of TAM were found to correlate with immunogenicity in two studies with rat transplanted tumors (Eccles and Alexander, 1974;Moore and Moore, 1977). This would suggest that the entry of blood monocytes into neoplastic tissues is mainly determined by specific antitumor immune responses. However, this hypothesis is not supported by observations in mouse sarcomas. Szymaniec and James (1976) found that the levels of TAM in a mouse sarcoma were unaffected by transplantation into thymus-deprived animals. , 1982). The present investigation was designed to elucidate whether culture supernatants of human and murine tumor cells indeed contain factor(s) chemotactic for mononuclear phagocytes, and to obtain indications as to...

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“…Although the myeloid-monocytic cells are morphologically similar, these cellular effectors are functionally heterogeneous and have critical roles in controlling or accelerating tumor growth and metastasis [1,2]. As such, clinical and immunologic outcomes are regulated based on the infiltrating cellular phenotype, including their stage of maturation and spatial location within tumors ( Fig.…”

mentioning

confidence: 99%

Inflammatory cell infiltration of tumors: Jekyll or Hyde

Talmadge

Donkor

Scholar

2007

Cancer Metastasis Rev

274

199

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Inflammatory cell infiltration of tumors contributes either positively or negatively to tumor invasion, growth, metastasis, and patient outcomes, creating a Dr. Jekyll or Mr. Hyde conundrum when examining mechanisms of action. This is due to tumor heterogeneity and the diversity of the inflammatory cell phenotypes that infiltrate primary and metastatic lesions. Tumor infiltration by macrophages is generally associated with neoangiogenesis and negative outcomes, whereas dendritic cell (DC) infiltration is typically associated with a positive clinical outcome in association with their ability to present tumor antigens (Ags) and induce Ag-specific T cell responses. Myeloid-derived suppressor cells (MDSCs) also infiltrate tumors, inhibiting immune responses and facilitating tumor growth and metastasis. In contrast, T cell infiltration of tumors provides a positive prognostic surrogate, although subset analyses suggest that not all infiltrating T cells predict a positive outcome. In general, infiltration by CD8(+) T cells predicts a positive outcome, while CD4(+) cells predict a negative outcome. Therefore, the analysis of cellular phenotypes and potentially spatial distribution of infiltrating cells are critical for an accurate assessment of outcome. Similarly, cellular infiltration of metastatic foci is also a critical parameter for inducing therapeutic responses, as well as establishing tumor dormancy. Current strategies for cellular, gene, and molecular therapies are focused on the manipulation of infiltrating cellular populations. Within this review, we discuss the role of tumor infiltrating, myeloid-monocytic cells, and T lymphocytes, as well as their potential for tumor control, immunosuppression, and facilitation of metastasis.

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Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice

Cited by 57 publications

References 26 publications

Sequential Study of Macrophage Migration Inhibition Factor in Renal Cell Carcinoma Patients

Sequential Study of Macrophage Migration Inhibition Factor in Renal Cell Carcinoma Patients

Chemotactic activity for mononuclear phagocytes of culture supernatants from murine and human tumor cells: Evidence for a role in the regulation of the macrophage content of neoplastic tissues

Inflammatory cell infiltration of tumors: Jekyll or Hyde

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