Exploring the Host Desmoplastic Response to Pancreatic Carcinoma

Abstract

The dramatic opportunities presented by comprehensive gene profiling technologies are curbed by the problem of segregating these large amounts of gene expression data into meaningful categories for study. This is particularly evident in infiltrating carcinomas of the pancreas, in which global gene expression data primarily mirrors the prominent desmoplastic response to the infiltrating neoplasm. In an effort to better characterize the gene expression of invasive pancreatic cancers and their associated desmoplastic response, we performed in situ hybridization on pancreatic cancer tissues to characterize the expression of 12 genes identified by serial analysis of gene expression as highly expressed in invasive pancreatic cancer tissues but not in pancreatic cancer cell lines. In situ hybridization demonstrated that eight genes were expressed within the stromal and/or angioendothelial cells of the desmoplastic response to the invasive tumor, and four of these genes were specifically expressed by the stromal cells immediately adjacent to the invasive neoplastic epithelium, suggesting regional differences in gene expression within the host desmoplastic response. In contrast, four genes were specifically expressed by the invasive neoplastic epithelium, indicating important differences between in vivo and in vitro gene expression of human epithelial neoplasms. We have identified a highly organized structure of gene expression within the host stromal response to invasive pancreatic cancer that may reflect tumor-host communication and serve as a target for therapeutic intervention.

Apolipoprotein C-1 maintains cell survival by preventing from apoptosis in pancreatic cancer cells

“…This is the first study that has found that ApoC-1 is highly expressed in pancreatic cancer cells but is faintly expressed in normal pancreatic ductal and stromal cells that surround cancerous cells. These findings are supported by studies indicating that ApoC-1 mRNA was highly expressed in pancreatic cancer tissues based on the serial analysis of gene expression analysis (Ryu et al, 2001;Iacobuzio-Donahue et al, 2002). We also found that ApoC-1 was expressed in the supernatant of medium used to culture pancreatic cancer cells.…”

The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

“…Yasui et al [23] found that ApoC-I was up-regulated in gastric cancer cells compared with normal gastric epithelial cells, on the basis of serial analysis of gene expression (SAGE). Christine et al [24] performed in situ hybridization of pancreatic tissue to characterize the expression of ApoC-I genes identified by SAGE and found that ApoC-I was highly expressed in invasive pancreatic cancer tissues. On the basis of these results, ApoC-I expression seems to be regulated in several types of cancers.…”

Serum Diagnosis of Pancreatic Adenocarcinoma Using Surface-Enhanced Laser Desorption and Ionization Mass Spectrometry

“…These peaks, however, were not among the top 2-4 discriminating peaks. Pancreatic cancer induces increases in a variety of serum markers including proteins derived from the neoplastic cells such as CA19 -9, from surrounding acini (as in the case of HIP/PAP), as well as from surrounding stroma that could include inflammatory or matrix markers (25,32,33). These results suggest that in the future separate marker panels may be used depending on whether the clinical question is to determine whether a healthy individual has a pancreatic abnormality that may be nonspecific but that could indicate the presence of a subclinical cancer or if the clinical question being asked is to differentiate pancreatic cancer from inflammatory pancreatic conditions.…”