Transfection of MDA-MB-231 human breast carcinoma cells with bone sialoprotein (BSP) stimulates migration and invasion in vitro and growth of primary and secondary tumors in nude mice

Abstract

We have investigated the role of bone sialoprotein (BSP), a secreted glycoprotein normally found in bone, in breast cancer progression. To explore functions for BSP in human breast cancer invasion and metastasis, the full-length BSP cDNA was transfected into the MDA-MB-231-BAG human breast cancer cell line under the control of the CMV promoter. Clones expressing BSP and vector control clones were isolated. BSP producing clones showed increased monolayer wound healing, a faster rate of stellate outgrowth in Matrigel and increased rate of invasion into a collagen matrix when compared to control clones. Clones were also examined in models of breast cancer growth and metastasis in vivo. BSP transfected clones showed an increased rate of primary tumor growth following mammary fat pad injection of nude mice. BSP transfected clones and vector control clones metastasized to soft organs and bone at a similar rate after intra-cardiac injection as determined by real-time PCR and X-ray analysis. Although these organs were targets for both BSP transfected and non-transfected cells, the size of the metastatic lesion was shown to be significantly larger for BSP expressing clones. This was determined by real-time PCR analysis for soft organs and by X-ray analysis of bone lesions. For bone this was confirmed by intra-tibial injections of cells in nude mice. We conclude that BSP acts to drive primary and secondary tumor growth of breast cancers in vivo.

Mechano-transduction mediated secretion and uptake of galectin-3 in breast carcinoma cells: Implications in the extracellular functions of the lectin

“…The stellate outgrowth in matrigel is typical of aggressive and invasive tumor cells [29]. Likewise the growth of 435 AS in matrigel is similar to the growth pattern of benign and non-metastatic cells in this extra cellular matrix.…”

“…The plaques in cells which express high levels of galectin-3, are suited for rapid cell spreading but looser adhesion to the substratum. These plaques may also be more suited for growth in vivo where the cells encounter substrata such as collagen, laminin, fibronectin and matrigel [29]. Although unrelated, a similar phenomenon occurs in the clustering of T-cell receptors.…”

Promotion of hematogenous metastatic potentials in human KB carcinoma cells with overexpression of cyclooxygenase-2

“…On the other hand, metastasis to liver by injection of tumor cells to portal vein or spleen (21,22) and metastasis to lung by injection of tumor cells to tail vein (20) are also reported as experimental metastasis models. Although an intra-cardiac injection of tumor cells (23,24) is easier to make metastasis than other models, it is uncommon because of the technical difficulty. When injected into the left cardiac ventricle of mice, KB/COX-2 developed metastases to multiple organ such as lung, stomach, femur and so on whereas KB/Neo was hardly found to develop metastases.…”

Les protéines SIBLING

“…Les trois isoformes a, b et c de l'OPN sont surexprimées au niveau de certains cancers, comme les gliomes de haut grade, avec une prédominance de la forme b qui augmente le potentiel invasif des cellules [18]. De la même façon, la transfection d'une lignée cellulaire cancéreuse mammaire, afin d'y surexprimer la BSP, stimule la migration et l'invasion in vitro [19].…”