Expression of S100P and Its Novel Binding Partner S100PBPR in Early Pancreatic Cancer

Abstract

S100P is a member of the S100 family of calcium-binding proteins and there have been several recent reports of its overexpression in pancreatic ductal adenocarcinoma (PDAC). We have used Far Western screening and in vitro interaction assays to identify and confirm a novel target protein for S100P. We have named this protein S100PBPR, and shown that its interaction with S100P is dependent on Ca(2+) or Mg(2+). S100PBPR was found to localize to cell nuclei where S100P is also present, and the two proteins co-immunoprecipitate. By in situ hybridization, S100PBPR transcript was found in islet cells but not duct cells of the healthy pancreas. Both S100P and S100PBPR were detected by quantitative real-time polymerase chain reaction in pancreatic intraepithelial neoplasia (PanIN) and PDAC samples, and in situ hybridization revealed the presence of S100PBPR transcript in malignant PDAC cells. These data suggest that an interaction between S100P and S100PBPR may be involved in early pancreatic cancer. S100P was further investigated in PanIN lesions and immunohistochemical analysis showed its expression to correlate significantly with increasing grade of PanINs, being found as early as PanIN-1 with more prevalent expression in PanIN-2 and -3. These data suggest that S100P can be added to the genetic progression model for PDAC.

Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features

“…24 S100P is expressed in nearly all cases of pancreatic adenocarcinoma and perihilar cholangiocarcinoma. 25,26 TFFs are peptides secreted by mucin-producing epithelial cells of the gastrointestinal tract involved in restitution and repair of the mucosa. 27 TFF1 is normally expressed in gastric mucosa and in the adenocarcinoma of many organs, including pancreatic adenocarcinoma.…”

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

“…The QRT-PCR and RT-PCR were conducted as described previously (Dowen et al, 2005). The primers used for the QRT-PCR were: forward 5 0 -CAGTTTTGCCCATTGAC CATG-3 0 and reverse 5 0 -ATAGCGCTGCGTTGTGGTG-3 0 and amplified a 71 bp amplicon.…”

S100P, a potential novel prognostic marker in colorectal cancer

“…S100P has been detected in a variety of tissues (19) and proven to play an important role in regulation of cell functions since its discovery in 1992 (12,13). It has become of special interest because of its ability to promote tumor invasion and metastasis (14,17,18).…”

“…S100 calcium-binding protein P (S100P), a member of S100 protein family, was first isolated from human placenta (12,13). The expression of S100P has been found in a number of tumors including pancreatic cancer cell lines and tissues (14,15), lung cancer, and it was correlated with immortalization of human breast epithelial cells in vitro and progression of breast cancer in vivo (16,17). S100P expression was associated with the grade of tumors, and it promoted tumor invasion and metastasis (14,17,18).…”

“…The expression of S100P has been found in a number of tumors including pancreatic cancer cell lines and tissues (14,15), lung cancer, and it was correlated with immortalization of human breast epithelial cells in vitro and progression of breast cancer in vivo (16,17). S100P expression was associated with the grade of tumors, and it promoted tumor invasion and metastasis (14,17,18). Expression of S100P was shown in CRC tissues compared with much less expression in normal mucosa (19)(20)(21), and it stimulated cancer cell growth and migration in vitro (20,21).…”