0121) (Fig. 1A). On the other hand, serum levels of APRIL in patients with PDAC were not significantly higher than in healthy subjects (7.7 �� 2.4 vs. 7.3 �� 2.2 pg/mL, respectively; p=0.895) (Fig. 1B). The increase in serum levels of BAFF was evaluated by UICC stage. Patients with UICC stage IV PDAC (T1-4, N0-1, M1) had significantly higher levels of serum BAFF than the patients with UICC stage more information Ib-III (2063 �� 1736 vs. 1186 �� 328 pg/mL, respectively; p=0.0182) (Fig. 1C). The clinical background of the patients at each stage is indicated in Table 2. Concerning the relationship between the serum levels of BAFF and PDAC tumor size, there was a significant positive correlation, as indicated in Fig. 1D (r=0.348; p<0.001). This suggested that the increase in serum levels of BAFF was associated with tumor growth and metastasis of PDAC.

Figure 1 Serum levels of BAFF and APRIL in patients with PDAC. Table 1 Clinical background of patients with pancreatic cancer and healthy subjects. Table 2 Clinical background of patients with pancreatic ductal adenocarcinoma. Expression of BAFF and BAFF-R in human PDAC tissue Immunohistochemistry experiments were performed to determine whether BAFF is expressed in pancreatic tissue. Pancreatic tissue from surgical species obtained from patients with PDAC was stained for BAFF and BAFF-R (Fig. 2 and and3).3). Tumor-infiltrating immune cells surrounding PDAC cells were found to remarkably express BAFF and BAFF-R (Fig. 2). Additional staining of CD20 (a marker of B lymphocytes), CD3 (T cell receptor, a marker of T lymphocytes) and CD68 (a marker of monocytes/macrophages) was performed to identify their types of infiltrating cells expressing BAFF or BAFF-R.

The distribution of BAFF- and BAFF-R-positive cells appeared consistent with the distribution of B lymphocytes, rather than that of T lymphocytes or monocyte/macrophages (Fig. 2). Recently, it has been shown that B lymphocytes can secrete BAFF [7], [8], [16]. Double immunofluorescence staining with BAFF and CD20, CD3, CD68 (Fig. 3A), and staining with BAFF-R and CD20, CD3, CD68 (Fig. 3B) was performed. The distribution of BAFF (green) and CD20 (red) was merged and appeared yellow (Fig. 3A). Moreover, the distribution of BAFF-R (green) and CD20 (red) was also merged and appeared yellow (Fig. 3B). However, the distribution of BAFF and BAFF-R were not co-localized with CD3 or CD68.

These results indicate that B lymphocytes, which express high levels of BAFF and BAFF-R, are in the infiltrate and proliferate in the tissue surrounding the PDAC. Figure 2 Immunohistochemistry of BAFF and BAFF receptor in human PDAC tissue. Drug_discovery Figure 3 Immunofluorescence of BAFF and BAFF receptor in human PDAC tissue. Expression of BAFF receptors in human PDAC tissues and human PDAC cell lines In order to investigate the expression of BAFF receptors in PDAC, immunohistochemistry was performed on PDAC tissues obtained from patients as well as on human PDAC cell lines.