Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis

Abstract

The classical fate of metastasizing breast cancer cells is to seed and form secondary colonies in bones. The molecules closely associated with these processes are predominantly present at the cell surface and in the extracellular space, establishing the first contacts with the target tissue. In this study, we had the rare opportunity to analyze a bone metastatic lesion and its corresponding breast primary tumor obtained simultaneously from the same patient. Using mass spectrometry, we undertook a proteomic study on cell surface and extracellular proteinenriched material. We provide a repertoire of significantly modulated proteins, some with yet unknown roles in the bone metastatic process as well as proteins notably involved in cancer cell invasiveness and in bone metabolism. The comparison of these clinical data with those previously obtained using a human osteotropic breast cancer cell line highlighted an overlapping group of proteins. Certain differentially expressed proteins are validated in the present study using immunohistochemistry on a retrospective collection of breast tumors and matched bone metastases. Our exclusive set of selected proteins supports the set-up of further investigations on both clinical samples and experimental bone metastasis models that will help to reveal the finely coordinated expression of proteins that favor the development of metastases in the bone microenvironment.

Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line

“…In these studies, bone-seeking MDA-MB-231 cells were compared with parental cells grown under in vitro culture conditions. Importantly, subsequent analysis has shown a close correlation in proteins changed between parental and bone-homing MDA-MB-231 cells grown in vitro and proteins changed between primary and bone-metastatic deposits of clinical samples acquired from the same patient (Dumont et al 2012). Therefore, alterations between parental and bone-homing variants of MDA-MB-231 cells are likely to be clinically relevant to breast cancer patients.…”

“…Therefore, it is likely that increased MMP9 and HRAS expression may drive bone colonisation through increasing the tumour cell extravasation once they reach their target metastatic organ (bone). Fibronectin, on the other hand, has well characterised properties as a cell adhesion molecule and has been shown to be upregulated in bone metastatic deposits compared with primary breast tumours (Dumont et al 2012). It is likely that increased expression of this molecule enables tumour cells to adhere to the stem cell niche once they have successfully entered the bone microenvironment (van der Pluijm et al 1997, Saad et al 2002.…”

Molecular alterations that drive breast cancer metastasis to bone

“…78 Fibronectin on the other hand has well-characterised properties as a cell adhesion molecule and has been shown to be upregulated in bone metastatic deposits compared with primary breast tumours. 79 It is therefore likely that increased expression of fibronectin enables tumour cells to adhere to the HSC niche once they have successfully entered the bone microenvironment. 60,68 MET and bone colonisation To enable colonisation of bone, tumour cells undergo a reverse EMT transition known as MET, reactivating their epithelial cell properties and increasing their adhesion and interactions with the bone marrow microenvironment 80,81 (Figure 4).…”

L’asporine : une nouvelle défense naturelle contre le cancer du sein

“…Nous avons développé une méthode permettant d'analyser les protéines tumorales accessibles spécifique-ment surexprimées au niveau de lésions cancéreuses humaines [3]. Nous avons appliqué cette méthode à divers types de cancers dont le cancer du sein [4,5], ce qui a conduit à la sélection de protéines systématiquement détectées et donc caractéristiques du tissu tumoral. Parmi ces protéines, on dénombre plusieurs …”