Serum levels of the angiogenic factor pleiotrophin in relation to disease stage in lung cancer patients

Abstract

Pleiotrophin is a heparin-binding growth factor involved in the differentiation and proliferation of neuronal tissue during embryogenesis, and also secreted by melanoma and breast carcinoma cells. Pleiotrophin exhibits mitogenic and angiogenic properties and has been shown to influence the vascular supply, expansion and metastasis of tumour cells. Our aim was to study the serum and plasma concentrations of pleiotrophin and the classical angiogenic growth factor vascular endothelial growth factor. Using a specific ELISA-test we studied patients with small cell lung cancer (n=63), and patients with non-small cell lung cancer (n=22) in comparison to healthy control subjects (n=41). In most of the lung cancer patients (81%), we found serum levels of pleiotrophin above those of control subjects (P50.001). Of the 63 small cell lung cancer patients in the study pleiotrophin serum levels were elevated in 55 cases (87%) and in 14 cases (63%) of the 22 non-small cell lung cancer patients. Pleiotrophin mean serum concentrations were 10.8-fold higher in the tumour patient group as compared to the control group (P50.001). Furthermore, pleiotrophin serum levels correlated positively with the stage of disease and inversely with the response to therapy. Plasma vascular endothelial growth factor concentrations were elevated in only in 28.6% of small cell lung cancer and 45.5% of non-small cell lung cancer patients by an average of 2.3-fold. Quite strikingly, there was no apparent correlation between the plasma vascular endothelial growth factor concentration and the stage of disease. Our study suggests that pleiotrophin may be an early indicator of lung cancer and might be of use in monitoring the efficacy of therapy, which needs to be confirmed by larger studies.

Ribozyme‐targeting reveals the rate‐limiting role of pleiotrophin in glioblastoma

“…Moreover, we observed a statistically significant reduction of PTN serum levels in animals with PTNdepleted U87 tumors. Concomitantly, we 18,45 and others 46 have previously shown elevated PTN levels in the serum of tumor patients, indicating that PTN serum levels correlate with PTN-positive tumors and that PTN, besides its functional role in tumor growth, may also serve as a prognostic marker. Further analysis of our tumor xenografts showed no differences with regard to proliferation within the tumors; however, the relevance of this finding remains unclear since the heterogeneity in proliferation within each tumor and each tumor section obscured the determination of the exact percentage of proliferating cells.…”

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

“…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.…”

The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer

“…Pleiotrophin is expressed in different human cancers [3][4][5][6][7][8][9][10][11], and recently, PTN was identified in different subtypes of human breast cancers [12][13][14]. Targeting of constitutive PTN signaling in human breast cancers that inappropriately express Ptn by a dominant negative PTN reverses their malignant phenotype both in vitro and in vivo [15].…”