Osteopontin: an effector and an effect of tumor metastasis

Abstract

Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; this is also reflected by increased levels of OPN in the circulation. Thus, increased OPN levels the plasma are an effect of tumor growth and progression. Functionally, high OPN levels are determinative of higher incidence of bone metastases in mouse models and are clinically correlated with metastatic bone disease and bone resorption in advanced breast cancer patients. Several research efforts have been made to therapeutically target and inhibit the activities of OPN. In this article we have reviewed OPN in its role as an effector of critical steps in tumor progression and metastasis, with a particular emphasis on its role in facilitating bone metastasis of breast cancer. We have also addressed the role of the host-derived OPN in influencing the malignant behavior of the tumor cells.

Fig. (1).

Schematic representation of the signaling pathways influenced by osteopontin. The phenotypes manifest as increased ability of cells to proliferate, migrate, survive and influence the development of tumor vasculature.

Fig. (2).

As compared to healthy women, women with metastatic breast cancer have higher median levels of circulating osteopontin. (Data adapted with permission from Clin Cancer Res 3: 605–611, 1997).

Fig. (3).

(A) Temporal increase in the level of plasma OPN in breast cancer patients with metastatic bone disease. (B) In patients with bone metastasis of breast cancer, higher OPN plasma levels are associated with poor survival. (Data adapted with permission from Endocrine-Related Cancer 11:771–779, 2004).

Fig. (4).

Osteopontin plays a role in the critical steps of tumor progression and metastasis. Depicted in this cartoon are the steps in metastasis culminating in colonization at the bone as a secondary site.

Fig. (5).

MDA-MB-435 cells that have been stably silenced for osteopontin by RNA interference show decreased heterotypic adhesion to hBME cells.