Macrophage‐induced cytotoxicity and anti‐metastatic activity of a 43‐kDa human urinary protein against the lewis tumor

Fontan, Élisabeth; Saklani, Hélène; Fauve, Robert M.

doi:10.1002/ijc.2910530124

Cited by 4 publications

(2 citation statements)

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“…Macrophage-mediated cytotoxicity was carried out as described (Fontan et al, 1993). Briefly, 3LL cells were pre-labeled for 24 hr with 2 µCi 125 I-UdR at 37°C, then washed 3 times to remove free radioactive nucleotides and re-suspended in D-MEM with 10% FCS.…”

Section: Cytotoxic Assaymentioning

confidence: 99%

The anti-tumoral activity of human glycoprotein HGP.92: A study with the mouse Lewis-lung-tumor cell

et al. 1997

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The ability of a purified human glycoprotein (HGP.92) to exert anti-tumor activity was investigated in a mouse model using long-term readout assays. In vitro, in the presence of inflammatory mouse macrophages incubated with HGP.92, the growth of the mouse Lewis-lung-tumor cells (3LL) was decreased. This effect was concentration-dependent and required direct contact between tumor targets and HGP.92-treated macrophages. In addition, if the macrophage mono-layer was depleted of HGP.92 before addition of the target cells, no more cytostatic effect was observed. This anti-tumor activity of HGP.92-treated mouse macrophage was partially abrogated by addition of catalase in the culture medium, but not by superoxide dismutase or scavengers of the hydroxyl radical and singlet oxygen. Moreover, this tumor-cell growth reduction was not dependent on nitric oxide. In vivo, multiple i.v. injections of HGP.92 (5 times, 3 days apart) during the first week and a half exerted significant anti-tumor activity, as assessed by the reduction of both the number and the size of the lung nodules 3 weeks after i.v. inoculation of 3LL cells. Int. J. Cancer, 70:0-0, 1997. r 1997 Wiley-Liss, Inc. We have shown that a human glycoprotein of 92 kDa (HGP.92), isolated and purified from human urine, protected normal and SCID mice against an otherwise lethal inoculum of Listeria monocytogenes given intravenously; in addition, inflammatory murine macrophages incubated in vitro with HGP.92 exert anti-tumoral activity, as assessed by the growth reduction of 3LL cells (Fontan et al., 1994). Sequencing of 5 tryptic peptides of HGP.92 revealed complete homology with the amino-acid sequence of the Tamm Horsfall glycoprotein (THP), a urinary oligomeric glycopro-tein consisting of 80-to 100-kDa sub-units. Treatment of THP with urea yields a monomeric molecule of 92 kDa, suggesting that HGP.92 could be a sub-unit of THP. THP is known to be produced in the kidney, but its physiological function remains unclear (Sikri et al., 1981; Kumar et al., 1985). Some authors have described immunosuppressive activity in vitro (Brown et al., 1986; Hession et al., 1987), but some have reported immunostimulatory effects on human lymphocytes (Hunt and McGiven, 1978; Yu et al., 1993) and polymorphonuclear neutrophils (Horton et al., 1990; Yu et al., 1992). In our experimental models, native oligomeric THP did not enhance the resistance of mice infected with L. monocytogenes, and mouse macrophages incubated in vitro with THP were not cytostatic against 3LL cells. The increased resistance of HGP.92-treated SCID mice to L. monocytogenes infection, as well as the anti-tumoral activity of HGP.92-treated macrophages, provide some evidence that macro-phages may be one of the targets of HGP.92 biological activity. Many studies indicate that mouse macrophages can be activated to a tumoricidal state in vitro and in vivo by various cytokines and by non-cytokine molecules such as lipopolysaccharide (LPS) acting either alone or in synergism. We therefore monitored the ability of HGP.92 to...

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Section: Cytotoxic Assaymentioning

confidence: 99%

The anti-tumoral activity of human glycoprotein HGP.92: A study with the mouse Lewis-lung-tumor cell

et al. 1997

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“…In vitro, HGP.43 induced cytotoxic activity in macrophages against Lewis carcinoma cells. In vivo, growth of the primary Lewis tumor was not delayed in HGP.43-treated mice, but the size and number of lung metastases were significantly reduced (5 Thymocytes were harvested from C3H/HeJ mice as described by Liao et al (9).…”

mentioning

confidence: 99%

A 92-kDa human immunostimulatory protein.

Fontan

Briend²,

Saklani-Jusforgues³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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We purified to apparent homogeneity a human urinary glycoprotein of 92 kDa (HGP.92) that, administered intravenously at 250 pg/kg, fully protected mice against a lethal inoculum of Listeria monocytogenes. Since HGP.92 protected scid mice, which lack B and T lymphocytes, this increased resistance toListeria did not appear to be lymphocyte mediated. Furthermore, inflammatory macrophages incubated with 6 nM HGP.92 inhibited the growth of Lewis carcinoma cells in vitro. These two activities appeared to depend on an oligosaccharlde moiety, as they were lost after N-Glycanase treatment of HGP.92. Thus, the biological activity of HGP.92 was in some way related to a glycan moiety. Thymocytes were harvested from C3H/HeJ mice as described by Liao et al. (9).Urinary Fractions. Twenty-four-hour urine specimens were collected from healthy male and female human beings and stored at -200C as described by Fontan et al. (4). THP was isolated from pooled urine after two salt precipitations as described by Tamm and Horsfall (10 tTo whom reprint requests should be addressed. 8353The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Some aspects of the macrophage-cancer relationship

Fauve

1993

Research in Immunology

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Macrophage‐induced cytotoxicity and anti‐metastatic activity of a 43‐kDa human urinary protein against the lewis tumor

Cited by 4 publications

References 15 publications

The anti-tumoral activity of human glycoprotein HGP.92: A study with the mouse Lewis-lung-tumor cell

The anti-tumoral activity of human glycoprotein HGP.92: A study with the mouse Lewis-lung-tumor cell

A 92-kDa human immunostimulatory protein.

Some aspects of the macrophage-cancer relationship

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