Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial.

Introduction: Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis.

Methods: We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/- octreotide in a randomized trial (NCIC CTG MA.

Human 21T breast epithelial cell lines mimic breast cancer progression in vivo and in vitro and show stage-specific gene expression patterns.

Early breast cancer progression involves advancement through specific morphological stages including atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (IMC), although not necessarily always in a linear fashion. Observational studies have examined genetic, epigenetic and gene expression differences in breast tissues representing these stages of progression, but model systems which would allow for experimental testing of specific factors influencing transition through these stages are scarce. The 21T series cell lines, all originally derived from the same patient with metastatic breast cancer, have been proposed to represent a mammary tumor progression series.

Lymphatic metastasis of breast cancer cells is associated with differential gene expression profiles that predict cancer stem cell-like properties and the ability to survive, establish and grow in a foreign environment.

Although lymphatic dissemination is a major route for breast cancer metastasis, there has been little work to determine what factors control the ability of tumor cells to survive, establish and show progressive growth in a lymph node environment. This information is of particular relevance now, in the era of sentinel lymph node biopsy, where smaller intranodal tumor deposits are being detected earlier in the course of disease, the clinical relevance of which is uncertain. In this study, we compared differentially expressed genes in cell lines of high (468LN) vs.

Downregulation of osteopontin contributes to metastasis suppression by breast cancer metastasis suppressor 1.

Breast cancer metastasis suppressor 1 (BRMS1) inhibits the ability of multiple human and murine cancer cell lines to metastasize to lymph nodes, bones and lungs. Comparison of mRNA expression in metastatic MDA-MB-435 human carcinoma cells (435) and metastasis-suppressed BRMS1 transfectants (435/BRMS1) showed a marked (>90%) reduction of osteopontin (OPN) mRNA and protein expression in BRMS1-overexpressing cells. OPN expression is associated with disease progression in patients, with higher levels of OPN produced by cancer cells associated with poorer patient survival.

The thrombin inhibitor Argatroban reduces breast cancer malignancy and metastasis via osteopontin-dependent and osteopontin-independent mechanisms.

Osteopontin (OPN) has been clinically and experimentally associated with breast cancer metastasis. Proteolytic cleavage of OPN by thrombin has been reported to increase its biologic activity. The purpose of this study was to determine if inhibition of thrombin could reduce the malignancy-promoting effects of OPN on breast cancer cell behavior in vitro and in vivo.

Role of the integrin-binding protein osteopontin in lymphatic metastasis of breast cancer.

Although a primary route of breast cancer metastasis is believed to be via lymphatics, the molecular factors involved are poorly understood. We hypothesized that one such factor may be the integrin-binding protein osteopontin (OPN), and we investigated this clinically and experimentally. In breast cancer patients undergoing sentinel lymph node biopsy, OPN levels were significantly higher in lymph node metastases than in the primary tumor (P < 0.

Expression of osteopontin and HGF/met in adult soft tissue tumors.

There is a need for molecular markers that predict biological behavior of adult soft tissue tumors. Elevated levels of osteopontin (OPN) a transformation-linked protein, have been associated with poor survival in many cancers. OPN induces cell migration in cancer cells, in part through activation of the hepatocyte growth factor (HGF) receptor (Met) and its signaling pathway.

A new model for lymphatic metastasis: development of a variant of the MDA-MB-468 human breast cancer cell line that aggressively metastasizes to lymph nodes.

Breast cancer often spreads from the primary tumor to regional lymph nodes. Lymph node status provides clinically important information for making treatment decisions. Spread via lymphatics is also important for the biology of breast cancer, as tumor cells in lymph nodes may provide a reservoir of cells leading to distant, lethal metastases.

Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model.

Metastatic spread, not primary tumor burden, is the leading cause of breast cancer deaths. For patient prognosis to improve, new systemic adjuvant therapies that are capable of effectively inhibiting the outgrowth of seeded tumor cells after surgical treatment of the primary breast tumor are needed. To facilitate the preclinical development of such therapies, relevant animal models of breast cancer metastasis that can mimic the postsurgical adjuvant setting are required.

Beta(3) integrin expression increases breast carcinoma cell responsiveness to the malignancy-enhancing effects of osteopontin.

Osteopontin (OPN) is a secreted phosphoprotein that has been associated with malignancy of breast and other cancers. OPN binds to several cell surface integrins including alpha(v)beta(3), alpha(v)beta(5), and alpha(v)beta(1). Although the relative contribution of these integrins to breast cancer cell malignancy is uncertain, correlative studies suggest that alpha(v)beta(3) may be particularly associated with increased tumor aggressiveness.