The Role of Osteopontin in Tumor Progression and Metastasis in Breast Cancer

Abstract

The use of cancer biomarkers to anticipate the outlines of disease has been an emerging issue, especially as cancer treatment has made such positive steps in the last few years. Progress in the development of consistent malignancy markers is imminent because advances in genomics and bioinformatics have allowed the examination of immense amounts of data. Osteopontin is a phosphorylated glycoprotein secreted by activated macrophages, leukocytes, and activated T lymphocytes, and is present in extracellular fluids, at sites of inflammation, and in the extracellular matrix of mineralized tissues. Several physiologic roles have been attributed to osteopontin, i.e., in inflammation and immune function, in mineralized tissues, in vascular tissue, and in kidney. Osteopontin interacts with a variety of cell surface receptors, including several integrins and CD44. Binding of osteopontin to these cell surface receptors stimulates cell adhesion, migration, and specific signaling functions. Overexpression of osteopontin has been found in a variety of cancers, including breast cancer, lung cancer, colorectal cancer, stomach cancer, ovarian cancer, and melanoma. Moreover, osteopontin is present in elevated levels in the blood and plasma of some patients with metastatic cancers. Therefore, suppression of the action of osteopontin may confer significant therapeutic activity, and several strategies for bringing about this suppression have been identified. This review looks at the recent advances in understanding the possible mechanisms by which osteopontin may contribute functionally to malignancy, particularly in breast cancer. Furthermore, the measurement of osteopontin in the blood or tumors of patients with cancer, as a way of providing valuable prognostic information, will be discussed based on emerging clinical data. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1087 -97)

Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

“…Although the mechanisms involved in the fibroblast responses remain obscure, the possibility that they are coordinated through interactions with ECM proteins is increasingly appreciated. OPN is a pleiotropic matricellular protein that is known to be involved in an array of biological processes including remodeling, metastasis, scarring, and inflammation (4,7,40,41,43,61). Several in vivo and in vitro studies suggested an important role of OPN in mesenchymal cell proliferation in vascular remodeling (31,32,37).…”

“…These proteins are abundantly expressed during development; however, in adulthood their production is mainly restricted to wound healing and tissue remodeling (7,25,34,36). Among these proteins, OPN is currently receiving the most attention in cancer and tissue repair (7,43,61). OPN was first described as a phosphoprotein secreted by malignant epithelial cells (50) but has now been shown to be secreted by many cell types, including osteoclasts, lymphocytes, macrophages, vascular smooth muscle cells, and cancer-associated fibroblasts.…”

Pre- and post-translational regulation of osteopontin in cancer

“…Full length OPN pre-mRNA consists of 7 exons (Rodrigues et al 2007) while OPN-b lacks exon 5 and OPN-c lacks exon 4 (Hijiya et al 1994;Kiefer et al 1989;Saitoh et al 1995;Young et al 1990) (Fig. 1).…”

The role of osteopontin expression in melanoma progression

“…In human malignant melanoma, OPN expression is significantly associated with reduced relapse-free survival and additional histological parameters that are associated with poor clinical outcome [7,24,29,33]. OPN is a prognostic marker in a variety of cancers [30,[39][40][41]. In metastatic and primary melanomas, OPN has also been suggested to be a novel promising biomarker for the detection of metastases in patients with primary melanomas [24,[42][43][44][45].…”

“…Several studies indicate that OPN protein is overexpressed in the majority of human cancers, including malignant melanoma, and is associated with tumor progression [14,[23][24][25][26][27][28][29][30]. Extensive microarray analyses of melanomas demonstrated that OPN also plays a role in melanoma progression [14,28,31,32].…”