Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prosta

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PLoS One. 2010 Oct 18;5(10):e13428.

Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells.

Gregory KJ, Zhao B, Bielenberg DR, Dridi S, Wu J, Jiang W, Huang B, Pirie-Shepherd S, Fannon M.

Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky, United States of America.

Abstract

BACKGROUND: Vitamin D binding protein-macrophage activating factor (DBP-maf) is a potent inhibitor of tumor growth. Its activity, however, has been attributed to indirect mechanisms such as boosting the immune response by activating macrophages and inhibiting the blood vessel growth necessary for the growth of tumors.

METHODS AND FINDINGS: In this study we show for the first time that DBP-maf exhibits a direct and potent effect on prostate tumor cells in the absence of macrophages. DBP-maf demonstrated inhibitory activity in proliferation studies of both LNCaP and PC3 prostate cancer cell lines as well as metastatic clones of these cells. Flow cytometry studies with annexin V and propidium iodide showed that this inhibitory activity is not due to apoptosis or cell death. DBP-maf also had the ability to inhibit migration of prostate cancer cells in vitro. Finally, DBP-maf was shown to cause a reduction in urokinase plasminogen activator receptor (uPAR) expression in prostate tumor cells. There is evidence that activation of this receptor correlates with tumor metastasis.

CONCLUSIONS: These studies show strong inhibitory activity of DBP-maf on prostate tumor cells independent of its macrophage activation.

Comments

Mikael Nordfors's picture

"Four prostate cancer cell lines were used in this study in order to include; the androgen sensitive (LNCaP) and insensitive (PC3M) lines, as well as highly metastatic lines (LNCaPLN3 and PC3MLN4) derived from each parental line, respectively."

"The four cell lines were then tested to determine their sensitivity to DBP-maf in proliferation studies. As shown in Figure 3A, DBP-maf at 1 µg/mL reduced proliferation to baseline levels or below in all cell lines with the exception of PC3M. It was interesting that, although the PC3M cells were not sensitive to DBP-maf in this assay, the metastatic clone PC3MLN4 had developed sensitivity to it."

Does this mean that androgen independent prostate cancer cells will not be very sensitive to GcMAF, meaning that in order to have effect, GcMAF treatment should be started before hormone treatment?