Oxysterol binding protein‐related protein‐5 is related to invasion and poor prognosis in pancreatic cancer

Abstract

In previous studies, the gene expression profiles of two hamster pancreatic cancer cells with different potentials for invasion and metastasis were analyzed. In the present study, we identified that one of the genes expressed strongly in the highly metastatic cell line is hamster oxysterol binding protein-related protein (ORP)-5. The aim of the present study was to clarify the relationship between ORP5 and invasion and poor prognosis of human pancreatic cancer. Invasion assays were carried out in both hamster and human pancreatic cancer cells by suppressing the ORP5 gene with short interfering RNA or inducing its expression by introducing an expression vector. To evaluate the relationship between ORP5 and the characteristics of human pancreatic cancer, 56 pancreatic cancer tissue specimens were analyzed and the ORP5 expression in each pancreatic cancer tissue specimen was analyzed by immunohistochemistry. In both the hamster and human pancreatic cancer cells, suppression of ORP5 significantly reduced the invasion rate of the cells and induction of ORP5 significantly enhanced the invasion rate of the cells. In the clinical sample, the median survival times of the patients with ORP5-positive (n = 33) and ORP5-negative (n = 23) cancer were 8.3 and 17.2 months, respectively (P = 0.02). Also, the 1-year survival rates of patients with ORP5-positive and ORP5-negative cancer were 36.4 and 73.9%, respectively (P = 0.005). The ORP5 expression level was related to both invasion and poor prognosis in human pancreatic cancer. These findings suggest that the expression of ORP5 may induce cancer cell invasion, resulting in the poor prognosis of pancreatic cancer. (Cancer Sci 2008; 99: 2387-2394) P ancreatic cancer is one of the most malignant tumors. In most cases, patients are already at an advanced stage of the disease at the time of diagnosis. The main reason for the poor prognosis is not only that these cancers are difficult to detect by ultrasonography or computed tomography, but also that they exhibit great potential for invasion and metastasis. To establish an effective treatment strategy for pancreatic cancer, it is necessary to clarify the cellular and molecular mechanisms of invasion and metastasis in pancreatic cancer.In our previous studies, we established two hamster pancreatic cancer cell lines with different potentials for invasion and metastasis: PC1, possessing a low potential for invasion and metastasis, and PC1.0, possessing a high potential for invasion and metastasis. These two cell lines were established from the same pancreatic ductal carcinoma induced by N-nitrosobis (2-oxopropyl) amine in a Syrian golden hamster.(1,2) Moreover, PC1.0 cell lines were found to produce a soluble proteinaceous factor in the medium; this factor was found to induce cell dissociation and therefore we designated it the 'dissociation factor'. (3)(4)(5) We hypothesized that isolation of this factor might provide great insight into the molecular and cellular mechanisms of pancreatic cancer invasion and metastasis, and we therefo...

Identification and evaluation of metastasis-related proteins, oxysterol binding protein-like 5 and calumenin, in lung tumors

“…These results suggested that OSBPL5, a metabolism-related molecule, might be involved in metastasis. Consistent with this notion, it was reported earlier that OSBPL5 expression is related to invasion and poor prognosis of pancreatic cancer (29,30). Thus, OSBPL5 may play a role in facilitating metastasis of lung cancer, similar to that suggested for pancreas cancer.…”

Noninvasive Screening Tests for Colorectal Cancer

“…Two kinds of RNA are detectable: mRNA, which codes for proteins, and microRNA, which influences gene expression. Table 1 shows a selected sample of both single and multiple fecal RNA markers [57,74,75,76,77,78]. With different markers and different isolation methods among these studies, the results suggest wide variation in sensitivity, but consistently high specificity.…”

ER –endosome contact sites: molecular compositions and functions

“…For instance, mutations in NPC1 and NPC2 are causative for the neurodegenerative Niemann–Pick disease, where cholesterol fails to reach the ER and accumulates in late endosomes (Mukherjee & Maxfield, ). Further, expression of ORP5 has been found to correlate with invasion and poor prognosis of pancreatic cancer (Koga et al , ), and expression of human ORP1L in macrophages enhances atherosclerotic lesion development in LDL receptor‐deficient mice (Yan et al , ). Overexpression of STARD3 induces liver damage in mice (Tichauer et al , ), and increased expression of this protein in human tumours is associated with high‐grade prostate cancer and HER2‐positive breast cancer (Vinatzer et al , ; Stigliano et al , ).…”