Type

Journal Article

Authors

Maria P Morgan
Fergal J O' Brien
Kerstin Pohl
Allan Jenkinson
Rachel F Cox

Subjects

Biochemistry

Topics
adenocarcinoma mammary neoplasms animal osteogenesis bone matrix animals tissue scaffolds real time calcification biomarkers tumor mice breast cancer calcification physiologic collagen type 1 cell proliferation dose response relationship cell line biomarkers real time polymerase chain reaction glycerophosphates humans bone morphogenetic protein 2 female neoplasm proteins animal collagen glycosaminoglycan scaffolds ascorbic acid cell line tumor dose response relationship drug collagen phosphates tumor life sciences mammary neoplasms physiologic drug

Osteomimicry of mammary adenocarcinoma cells in vitro; increased expression of bone matrix proteins and proliferation within a 3D collagen environment. (2012)

Abstract Bone is the most common site of metastasis for breast cancer, however the reasons for this remain unclear. We hypothesise that under certain conditions mammary cells possess osteomimetic capabilities that may allow them to adapt to, and flourish within, the bone microenvironment. Mammary cells are known to calcify within breast tissue and we have recently reported a novel in vitro model of mammary mineralization using murine mammary adenocarcinoma 4T1 cells. In this study, the osteomimetic properties of the mammary adenocarcinoma cell line and the conditions required to induce mineralization were characterized extensively. It was found that exogenous organic phosphate and inorganic phosphate induce mineralization in a dose dependent manner in 4T1 cells. Ascorbic acid and dexamethasone alone have no effect. 4T1 cells also show enhanced mineralization in response to bone morphogenetic protein 2 in the presence of phosphate supplemented media. The expression of several bone matrix proteins were monitored throughout the process of mineralization and increased expression of collagen type 1 and bone sialoprotein were detected, as determined by real-time RT-PCR. In addition, we have shown for the first time that 3D collagen glycosaminoglycan scaffolds, bioengineered to represent the bone microenvironment, are capable of supporting the growth and mineralization of 4T1 adenocarcinoma cells. These 3D scaffolds represent a novel model system for the study of mammary mineralization and bone metastasis. This work demonstrates that mammary cells are capable of osteomimicry, which may ultimately contribute to their ability to preferentially metastasize to, survive within and colonize the bone microenvironment.
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Full list of authors on original publication

Maria P Morgan, Fergal J O' Brien, Kerstin Pohl, Allan Jenkinson, Rachel F Cox

Experts in our system

1
Maria P Morgan
Royal College of Surgeons in Ireland
Total Publications: 27
 
2
Kerstin Pohl
Royal College of Surgeons in Ireland