Serum pleiotrophin levels are elevated in multiple myeloma patients and correlate with disease status

Abstract

SummaryPleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparinbinding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple myeloma (MM) patients when compared with healthy subjects (P < 0AE0001). Serum levels of this protein significantly increased during progression of disease, and decreased during response to anti-MM therapy (P < 0AE001). These results suggest that serum PTN may be a new biomarker for monitoring the disease status and therapeutic response of MM patients.

Pleiotrophin is highly expressed by myeloma cells and promotes myeloma tumor growth

“…33 We discovered that PTN is increased in the serum from MM patients and that the levels correlate with disease status. 34 Here we report that the malignant plasma cells from MM patients as well as MM cell lines produce and secrete PTN. Moreover, we demonstrate that a polyclonal anti-PTN antibody reduces MM cell growth and enhances apoptosis in vitro and inhibits the growth of human myeloma tumors in immunodeficient mice.…”

Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis

“…49,52 However, the origin of cells that ultimately line tumor blood vessels and specific proteins required for tumor vasculogenesis remain unclear. or CD14 ϩ cells alone or exposed to M-CSF, the PTN-producing MM cell lines U266 and RPMI8226, or serum from a healthy control subject or a patient with PCL containing high levels of PTN (3.4 ng/mL) 22 were analyzed for gene expression using primers specific for VWF, Tie-2, Flk-1, and GAPDH with RT-PCR. (F) Endothelial cells (HCAECs) or CD14 ϩ cells alone or exposed to M-CSF, the PTN-producing MM cell line U266, or BM from a healthy control subject or serum from the patient with PCL were analyzed for expression of the VWF, Tie-2, and Flk-1 genes in the presence of anti-PTN or isotype-matched control antibodies.…”

“…Supernatants were obtained from the culture medium after 48 hours for determination of PTN concentrations as determined by enzyme-linked immunosorbent assay (ELISA) as described previously 22 and performed in triplicate.…”

“…17,20 We have recently demonstrated that PTN is expressed and secreted by the malignant plasma cells from MM patients. 21,22 Serum levels of PTN are elevated in cancer patients including MM, and the amount of this protein correlates with the patient's disease status and response to treatment. [22][23][24] Anti-PTN antibody treatment reduces growth and enhances apoptosis of MM cell lines and fresh tumor cells from MM patients in vitro.…”

“…21,22 Serum levels of PTN are elevated in cancer patients including MM, and the amount of this protein correlates with the patient's disease status and response to treatment. [22][23][24] Anti-PTN antibody treatment reduces growth and enhances apoptosis of MM cell lines and fresh tumor cells from MM patients in vitro. 21 Importantly, this antibody also suppresses the growth of MM in vivo using a severe combined immunodeficiency (SCID)-hu murine model.…”