Abstract
BackgroundBMPs are currently receiving attention for their role in tumorigenesis and tumor progression. Currently, most BMP expression studies are performed on carcinomas, and not much is known about the situation in sarcomas.Methodology/Principal FindingsWe have investigated the BMP expression profiles and Smad activation in clones from different spontaneous canine mammary tumors. Spindle cell tumor and osteosarcoma clones expressed high levels of BMPs, in particular BMP-2, -4 and -6. Clones from a scirrhous carcinoma expressed much lower BMP levels. The various clones formed different tumor types in nude mice but only clones that expressed high levels of BMP-6 gave bone formation. Phosphorylated Smad-1/5, located in the nucleus, was detected in tumors derived from clones expressing high levels of BMPs, indicating an active BMP signaling pathway and BMP-2 stimulation of mammary tumor cell clones in vitro resulted in activation of the Smad-1/5 pathway. In contrast BMP-2 stimulation did not induce phosphorylation of the non-Smad pathway p38 MAPK. Interestingly, an increased level of the BMP-antagonist chordin-like 1 was detected after BMP stimulation of non-bone forming clones.Conclusions/SignificanceWe conclude that the specific BMP expression repertoire differs substantially between different types of mammary tumors and that BMP-6 expression most probably has a biological role in bone formation of canine mammary tumors.
Highlights
Bone morphogenetic proteins (BMPs), members of the TGF-b superfamily, constitute a group of extracellular factors that are important in many cellular processes
To study the BMP expression profile in mammary tumors of different types, cell lines were established from a spindle cell tumor (CMT-U309), an osteosarcoma (CMT-U353B) and a scirrhous carcinoma (CMT-U353 H4) of canine origin
This study is, to our knowledge, the first in which the expression profile for BMPs in different types of canine mammary tumors is determined in concert, some studies have addressed the expression of individual BMPs in selected types of mammary tumors and cell lines [12,28,29,30,31]
Summary
Bone morphogenetic proteins (BMPs), members of the TGF-b superfamily, constitute a group of extracellular factors that are important in many cellular processes. They were named due to their ability to induce bone formation [1], but it is well recognized that BMPs can participate in numerous other processes [2]. There is currently an interest for BMPs in relation to mammary tumors, [11,12] and metastases derived from human breast cancer often localize to bone [13], whereas this is uncommon in dogs [14,15]. Most BMP expression studies are performed on carcinomas, and not much is known about the situation in sarcomas
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