Role Of Osteopontin In Cancer Research Articles

The multidirectional role of osteopontin in cancer

Osteopontin (OPN) was described for the first time as a potential marker of neoplastic transformation by Senger et al . in 1979. Studies suggesting an important role of OPN in oncology, allergology, nephrology and cardiology have been published for many years. However, the largest number of articles pertains to the role of OPN in neoplastic transformation and will surely facilitate future determination of OPN levels in blood or cancer tissues with the pur­pose of disease diagnosing, staging, prognosing metastases and monitoring the treatment effectiveness. Numerous studies showed that high OPN expression levels accompany metastases formation; the protein was also confirmed to be involved in stimulation of cell proliferation and formation of new blood vessels, i.e. angiogenesis. OPN was also shown to be capable of binding the CD-44 receptors, which facilitates migration and invasion of cancer cells into the blood vessels. Correlation was also demonstrated between OPN expression and the time to disease recurrence and overall survival in patients with breast cancer, gastric cancer, hepatocellular cancer, hormone-depen­dent prostate cancer, kidney cancer and endometrial cancer. The exact mechanism responsible for OPN’s role in neoplastic transformation remains unclear and numerous research studies are conducted in this area.

Osteopontin-Enhanced Hepatic Metastasis of Colorectal Cancer Cells

Liver metastasis is a major cause of mortality from colorectal cancer (CRC). However, mechanisms underlying this process are largely unknown. Osteopontin (OPN) is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6) was detected by using an immunohistochemical (IHC) method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Florescence redistribution after photobleaching (FRAP) was used to study gap functional intercellular communication (GJIC) among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

Asbestos Exposure and Serum Osteopontin

To the Editor: Pass et al. (Oct. 13 issue)1 report that elevated osteopontin levels in workers with pleural disease who have been exposed to asbestos support a diagnosis of mesothelioma. The authors acknowledge that other cancers express osteopontin, and they mention the need for further studies. The expression of osteopontin in numerous benign inflammatory and fibrotic lung diseases,2 which considerably limits the potential use of osteopontin as a tumor marker, was not discussed. In addition to the osteopontin levels associated with lung carcinoma, similar levels are seen in tuberculosis, interstitial lung diseases, and cardiac disease.2,3 These clinical entities pose diagnostic difficulties in patients with asbestosrelated pleural disease. Therefore, measurement of osteopontin levels is unlikely to help diagnostically in this clinical scenario. The functional diversity of osteopontin in part reflects allelic variation and extensive post-translational modification.2 Certain isoforms of osteopontin have differing biologic functions.4 Tumorderived osteopontin functions in a manner distinct from non–tumor-derived osteopontin.5 Much as specific isoforms may account for the role of osteopontin in cancer, future studies may define variants with higher diagnostic potential. Until then, the specificity of osteopontin measurement is too low for it to be used as a screening tool for mesothelioma. Anthony W. O’Regan, M.D. National University of Ireland, Galway Galway, Ireland anthony.oregan@whb.ie