Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages.

Mornex, J. F.; Martinet, Yves; Yamauchi, Kiyomi; Bitterman, Peter B.; Grotendorst, Gary R.; Chytil-Weir, A; Martin, George R.; Crystal, Ronald G.

doi:10.1172/jci112574

Cited by 130 publications

(51 citation statements)

References 40 publications

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“…tinct growth factors that bind to heparin. One of these HBGFs elutes from immobilized heparin with 0.5 M NaCI and can be shown to be PDGFlike, confirming earlier reports of macrophagederived PDGF (Shimokado et al, 1985;Mornex et al, 1986). The evidence that the HBGF eluting at 0.5 M NaCI is PDGF-like includes coelution with human PDGF on immobilized heparin columns, neutralization of growth activity by antisera that neutralize PDGF, inactivation by disulfide reducing agents, and resistance to heating at 100°C.…”

Section: Introductionsupporting

confidence: 84%

“…Macrophages produce many growth factors, possibly more than any other cell type. Among the well-characterized macrophage-derived growth factors are platelet-derived growth factor (PDGF) (Shimokado et al, 1985;Mornex et al, 1986), basic fibroblast growth factor (bFGF) (Baird et al, 1985), transforming growth factoralpha (TGF-a) (Madtes et al, 1988), transforming growth factor-beta (TGF-fl) (Assoian et al, 1987), interleukin-1 (IL-1) (Hazuda et al, 1988;Schmidt et al, 1984), and tumor necrosis factoralpha (TN F-a) (Leibovich et al, 1988). Additional macrophage-derived growth factors have been reported but they have yet to be fully characterized and purified (Madtes et aL, 1988;Singh et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…It is not neutralized by anti-PDGF antisera, suggesting that it is not a PDGF-like growth factor. At 1-2 d in culture, it is difficult to ascertain the cellular origin of these two HBGFs because at this point mononuclear cell preparations are contaminated by other cells such as platelets, which are known producers of growth factors such as PDGF (Shimokado et aL, 1985;Mornex et al, 1986) and platelet-derived endothelial cell growth factor (PD-ECGF) (Ishikawa et al, 1989). In general, there is about one to five times more PDGF compared with the higher affinity-binding HBGF in the conditioned medium of 1-2-d-old mononuclear cells.…”

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of a macrophage-derived heparin-binding growth factor.

1990

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Human mononuclear cells were plated in culture, and the conditioned media of these cells were analyzed by heparin-Sepharose affinity chromatography. The fractions were tested for growth factor activity as measured by the stimulation of DNA synthesis in BALB/c 3T3 cells. After 2 d in culture, two peaks of heparin-binding growth factor (HBGF) activity were detected, one eluting with 0.5 M NaCI, which could be shown to be platelet-derived growth factor (PDGF)-like, and the other eluting with 1.0 M NaCI. After 7-11 d in culture, when monocytes had clearly differentiated into macrophages, >95% of the HBGF activity in conditioned medium consisted of the 1.0 M NaCI elution peak. This activity, which was designated macrophage-derived HBGF (MD-HBGF), was found to be a cationic heat-resistant polypeptide with a molecular weight in the range of 14-25 kDa. Analysis using Western blots and specific neutralizing antisera, as well as comparative heparin affinity analysis, indicated that MD-HBGF was not identical to other heparin-binding 3T3 cell growth factors known to be produced by macrophages, such as PDGF (AB, AA, and BB forms), acidic fibroblast growth factor, and basic fibroblast growth factor. In addition to stimulating mitogenesis in 3T3 cells, MD-HBGF also stimulated the proliferation of vascular smooth muscle cells, but did not stimulate the proliferation of vascular endothelial cells.

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Section: Introductionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Isolation and characterization of a macrophage-derived heparin-binding growth factor.

1990

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“…Macrophages might therefore be implicated in promoting tumour growth in these circumstances but the point is not proven. If this potentiation were secondary to the increased numbers of macrophages then it might be because of the many types of polypeptide growth factors they produce -including PDGF and EGF (Leslie et al, 1984;Hamburger & White, 1986;Nordan & Potter, 1986;Morne et al, 1986;Rich, 1986).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of organ selective tumour growth by bloodborne cancer cells

Murphy

Alexander²,

Senior³

et al. 1988

Br J Cancer

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Summary The sites of tumour development for 6 rat tumours injected into syngeneic rats via different vascular routes was determined. Xenografts of human tumours were also injected intra-arterially (i.a.) into immunosuppressed rats.Following intravenous (i.v.) In explaining the mechanism of site selectivity by bloodborne metastasis the haemodynamic theory of Ewing (1928) stressed the importance of the mechanics of the circulation whereas the Soil/Seed hypothesis of Paget (1889) emphasized the importance of the environment in which the trapped emboli found themselves. The eventual sites of metastasis are, however, determined by both haemodynamic and soil/seed factors. Haemodynamic factors are important following the venous discharge of tumour cells since the 'organs of first encounter' are the commonest site for bloodborne metastasis -the lung after systemic venous discharge of tumour cells and the liver after portal venous discharge (Viadana et al., 1978). The present study emphasizes that the 'soil' becomes important when tumour cells have entered the systemic arterial circulation and are thereby delivered to all organs. Clinically this situation can occur when cells are released from primary or secondary lung tumours or possibly when cells released into the venous circulation manage to traverse the lung capillaries.In this paper we extend earlier data (Murphy et al., 1986) on the pattern of spread of rat syngeneic non-lymphoid and non-haemopoietic tumours following intravenous (i.v.), intraportal (i.ptl.) and intra-arterial (i.a.) injection. In our i.v. and i.ptl. studies as well as previously reported studies tumour growth is essentially limited to the 'organs of first encounter' and the study of mechanisms of site selectivity is therefore limited. In order to deliver tumour cells to all organs we have injected them intra-arterially via the intracardiac (i.c.) route. Labelled cell distribution after i.c. injection has been compared with the distribution of cardiac output (measured using the microsphere technique) in order to establish whether cells disseminate and arrest passively or whether they recirculate and localise in certain organs. The 'arterial pattern' of tumour growth after unlabelled cell injection has then been compared with the arterial distribution of labelled tumour cells to establish and quantitate the 'soil effect'.Having established a 'soil effect' after arterial injection of tumour cells we have attempted to determine the mechanisms using several approaches. Firstly a correlation of site selectivity with organ vascularity (using data obtained from the microsphere studies) was sought since there have been reports that more vascular organs might be more susceptible to metastasis (Weiss et al., 1981). Secondly the rate of autolysis of trapped labelled cells in different organs has been compared with the organs susceptibility to tumour growth. Thirdly we have intervened pharmacologically to see if site preference can be altered and finally we have rendered refractory organs susceptible to tum...

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“…Other studies have shown that activated human alveolar macrophage secrete PDGFs Mornex et al, 1986;Shimokado et al, 1985). Thus, postnatally, PDGF appears to be one of the factors available to the alveolar macrophage for mediating normal lung defense and lung in¯ammation .…”

Section: Discussionmentioning

confidence: 94%

Modification of PDGFα receptor expression or function alters the metastatic phenotype of 3LL cells

Fitzer‐Attas

Feigelson

et al. 1997

Oncogene

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Functional PDGFa receptors are selectively expressed on highly lung-metastasizing clones of the 3LL Lewis lung carcinoma, but not on low-mestastatic clones. The highly metastatic clones are also growth induced in vitro by PDGF and lung conditioned medium. To investigate whether modi®cation of PDGFa receptor expression or function can a ect metastatic capability, we transfected cells of a low-metastatic 3LL clone with a full length PDGFa receptor gene and cells of a highly-metastatic clone with a truncated kinase domain PDGFa receptor gene. Introduction of the full length PDGFa receptor conferred upon low-metastatic cells the ability to grow in vitro in the presence of PDGF-AA and to colonize the lung in experimental and spontaneous metastases assays. Conversely, introduction of a truncated version of the PDGFa receptor into highly metastatic cells reduced their metastatic load to control levels. Accordingly, their responses to PDGF-AA, including growth stimulation and receptor autophosphorylation, were reduced. These results demonstrate that PDGFa receptor expression and function can control the capacity of tumor cells to generate metastases in the lung. The response of this receptor to lung-derived PDGF-like factors may de®ne a paracrine mode of metastatic cell growth in the target organ.

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Spontaneous expression of the c-sis gene and release of a platelet-derived growth factorlike molecule by human alveolar macrophages.

Cited by 130 publications

References 40 publications

Isolation and characterization of a macrophage-derived heparin-binding growth factor.

Isolation and characterization of a macrophage-derived heparin-binding growth factor.

Mechanisms of organ selective tumour growth by bloodborne cancer cells

Modification of PDGFα receptor expression or function alters the metastatic phenotype of 3LL cells

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