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Secretion of soluble complement inhibitors factor H and factor H-like protein (FHL-1) by ovarian tumour cells.

Junnikkala S, Hakulinen J, Jarva H, Manuelian T, Bjørge L, Bützow R, Zipfel PF, Meri S - Br. J. Cancer (2002)

Bottom Line: We observed that the soluble complement regulators factor H and factor H-like protein were abundantly present in ascites samples as well as in primary tumours of patients with ovarian cancer.In ascites samples the mean level of factor H-like protein (130+/-55 microg ml(-1)) was 5.5-fold higher than in normal human serum (24+/-3 microg ml(-1)).Subsequently, the PA-1 and SW626 cell lines were found to secrete a soluble form of the membrane cofactor protein (CD46).

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology and Immunology, Haartman Institute, University Central Hospital, FIN-0014 Helsinki, Finland.

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Factor H/FHL-1 binding to ovarian tumour cells. (A) Binding of 125I-labelled factor H and FHL-1 to ovarian tumour cells SW626, PA-1, SK-OV-3 and Caov-3. Cells (93×105) were incubated with radiolabelled factor H (30 ng, 6.6×106 c.p.m. μg−1) or FHL-1 (30 ng, 3.3×106 c.p.m. μg−1) for 1 h at 37°C in 1 : 3 GVBS, pH 7.4. The results (mean±s.d.; n=3) are expressed as the amount of bound protein (ng). A representative of three experiments with similar results is shown. (B) Dose-response analysis of binding of 125I-labelled factor H and FHL-1 to SK-OV-3 cells. (C) Inhibition analysis of binding of 125I-labelled factor H to SK-OV-3 cells. Indicated amounts of unlabelled factor H or BSA (up to a 100-fold excess) were incubated together with 125I-labelled factor H as in (A).
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fig4: Factor H/FHL-1 binding to ovarian tumour cells. (A) Binding of 125I-labelled factor H and FHL-1 to ovarian tumour cells SW626, PA-1, SK-OV-3 and Caov-3. Cells (93×105) were incubated with radiolabelled factor H (30 ng, 6.6×106 c.p.m. μg−1) or FHL-1 (30 ng, 3.3×106 c.p.m. μg−1) for 1 h at 37°C in 1 : 3 GVBS, pH 7.4. The results (mean±s.d.; n=3) are expressed as the amount of bound protein (ng). A representative of three experiments with similar results is shown. (B) Dose-response analysis of binding of 125I-labelled factor H and FHL-1 to SK-OV-3 cells. (C) Inhibition analysis of binding of 125I-labelled factor H to SK-OV-3 cells. Indicated amounts of unlabelled factor H or BSA (up to a 100-fold excess) were incubated together with 125I-labelled factor H as in (A).

Mentions: The immunohistochemical evidence of tumour-associated factor H/FHL-1 suggested that the ovarian tumour cells could carry surface components that bind factor H and/or FHL-1, proteins which both have binding sites for glycosaminoglycans and other polyanions. In accordance, we found that all the ovarian tumour cell lines SK-OV-3, Caov-3, PA-1 and SW626 bound both 125I-labelled factor H and FHL-1 to their cell surfaces (Figure 4AFigure 4


Secretion of soluble complement inhibitors factor H and factor H-like protein (FHL-1) by ovarian tumour cells.

Junnikkala S, Hakulinen J, Jarva H, Manuelian T, Bjørge L, Bützow R, Zipfel PF, Meri S - Br. J. Cancer (2002)

Factor H/FHL-1 binding to ovarian tumour cells. (A) Binding of 125I-labelled factor H and FHL-1 to ovarian tumour cells SW626, PA-1, SK-OV-3 and Caov-3. Cells (93×105) were incubated with radiolabelled factor H (30 ng, 6.6×106 c.p.m. μg−1) or FHL-1 (30 ng, 3.3×106 c.p.m. μg−1) for 1 h at 37°C in 1 : 3 GVBS, pH 7.4. The results (mean±s.d.; n=3) are expressed as the amount of bound protein (ng). A representative of three experiments with similar results is shown. (B) Dose-response analysis of binding of 125I-labelled factor H and FHL-1 to SK-OV-3 cells. (C) Inhibition analysis of binding of 125I-labelled factor H to SK-OV-3 cells. Indicated amounts of unlabelled factor H or BSA (up to a 100-fold excess) were incubated together with 125I-labelled factor H as in (A).
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fig4: Factor H/FHL-1 binding to ovarian tumour cells. (A) Binding of 125I-labelled factor H and FHL-1 to ovarian tumour cells SW626, PA-1, SK-OV-3 and Caov-3. Cells (93×105) were incubated with radiolabelled factor H (30 ng, 6.6×106 c.p.m. μg−1) or FHL-1 (30 ng, 3.3×106 c.p.m. μg−1) for 1 h at 37°C in 1 : 3 GVBS, pH 7.4. The results (mean±s.d.; n=3) are expressed as the amount of bound protein (ng). A representative of three experiments with similar results is shown. (B) Dose-response analysis of binding of 125I-labelled factor H and FHL-1 to SK-OV-3 cells. (C) Inhibition analysis of binding of 125I-labelled factor H to SK-OV-3 cells. Indicated amounts of unlabelled factor H or BSA (up to a 100-fold excess) were incubated together with 125I-labelled factor H as in (A).
Mentions: The immunohistochemical evidence of tumour-associated factor H/FHL-1 suggested that the ovarian tumour cells could carry surface components that bind factor H and/or FHL-1, proteins which both have binding sites for glycosaminoglycans and other polyanions. In accordance, we found that all the ovarian tumour cell lines SK-OV-3, Caov-3, PA-1 and SW626 bound both 125I-labelled factor H and FHL-1 to their cell surfaces (Figure 4AFigure 4

Bottom Line: We observed that the soluble complement regulators factor H and factor H-like protein were abundantly present in ascites samples as well as in primary tumours of patients with ovarian cancer.In ascites samples the mean level of factor H-like protein (130+/-55 microg ml(-1)) was 5.5-fold higher than in normal human serum (24+/-3 microg ml(-1)).Subsequently, the PA-1 and SW626 cell lines were found to secrete a soluble form of the membrane cofactor protein (CD46).

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology and Immunology, Haartman Institute, University Central Hospital, FIN-0014 Helsinki, Finland.

Show MeSH
Related in: MedlinePlus