Pleiotrophin Expression in Human Pancreatic Cancer and Its Correlation with Clinicopathological Features, Perineural Invasion, and Prognosis

Abstract

Pleiotrophin (PTN), a heparin-binding growth factor also known as neurite growth-promoting factor, exhibits several properties related with tumor development. PTN and its receptor, N-syndecan, may play a very important role in tumor growth and neural invasion of pancreatic cancer. We investigated PTN and N-syndecan protein levels in 38 patients with pancreatic cancer by immunohistochemistry, and analyzed for its correlation with clinicopathological features, perineural invasion, and prognosis. The results showed that PTN and N-syndecan proteins were found in 24 (63.2%) and 22 (57.9%) specimens, respectively. PTN and N-syndecan expressions were associated with perineural invasion (P = 0.016 and P = 0.029, respectively). High PTN expression was closely related to an advanced TNM stage (P = 0.007), lymph node metastasis (P = 0.040), and decreased postoperative survival at 3 years (50.0% versus 20.8%, respectively; P = 0.001). We conclude that high expression of PTN combined with N-syndecan may contribute to the increased perineural invasion and poor prognosis of pancreatic cancer.

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer

“…It has been reported that the binding of PTN with N-syndecan in pancreatic nerves promotes the development of neurites[30]. Malignant pancreatic cancer cells penetrate and damage the perineurium of pancreatic nerves.…”

“…Neuronal damage disrupts neural homeostasis. A study by Yao et al[30] proposed a potential repair of the pancreatic nerves by the growth of additional neurons generated by neurons and Schwann cells. Nevertheless, more PTN positive cancer cells could invade the injured site because of the increased levels of N-syndecan.…”

Using Gene Expression to Predict Differences in the Secretome of Human Omental vs. Subcutaneous Adipose Tissue

“…PTN is a 136‐amino‐acid‐long secreted cytokine related to diverse biological processes, including neuritis outgrowth, angiogenesis, expansion, and metastasis of tumor cells (35). Elevated PTN expression has been found to act as an essential autocrine, paracrine, and angiogenic factor for various cancers (36). PTN has been shown to induce the production of various cytokines including tumor necrosis factor‐α, IL‐1β, IL‐6, IL‐2, and IL‐12 in peripheral blood mononuclear cells (37) and therefore in adipose tissue it may be involved in the proinflammatory response associated with obesity (3).…”

PTN (pleiotrophin)

“…High levels of PTN have been detected in several cancers and cell lines derived from these tumours. Examples of such malignancies include breast (Wellstein et al, 1992;Riegel and Wellstein, 1994;Choudhuri et al, 1997;Chang et al, 2007), prostate (Vacherot et al, 1999;Hatziapostolou et al, 2005), cervical (Moon et al, 2003), colon (Souttou et al, 1998;Kong et al, 2012), pancreatic (Weber et al, 2000;Yao et al, 2009), lung (Garver et al, 1993;Jäger et al, 1997;Feng et al, 2010), and ovarian (Nakanishi et al, 1997;Collino et al, 2009;Lee et al, 2012) carcinomas, gliomas (Powers et al, 2002;Ulbricht et al, 2003;Zhang et al, 2004;Grzelinski et al, 2005;Lu et al, 2005;Grzelinski et al, 2006;Ulbricht et al, 2006;Peria et al, 2007;Mikelis et al, 2009), meningiomas (Mailleux et al, 1992), melanomas (Czubayko et al, 1996;Satyamoorthy et al, 2000;Seykora et al, 2003;Wu et al, 2005;Gao et al, 2011), multiple myeloma (Chen et al, 2007;Chen et al, 2009), choriocarcinoma (Schulte et al, 1996), and most cell lines of malignant pediatric tumours (Barthlen et al, 2003).…”

“…It has been shown that patients with pancreatic or colon cancer have elevated serum PTN levels (Souttou et al, 1998;Kong et al, 2012), which drop after successful tumour removal (Souttou et al, 1998). PTN expression is increased in pancreatic cancer tissues compared to inflammatory or normal tissues (Klomp et al, 2002) and may be also linked to the increased perineural invasion and poor prognosis of pancreatic cancer (Yao et al, 2009). PTN has been also mentioned as a new diagnostic marker for testicular cancer with high sensitivity even in early-stage testicular cancer (Aigner et al, 2003).…”